Molecule Information

General Information of the Molecule (ID: Mol01839)
Name
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) ,Homo sapiens
Synonyms
Proto-oncogene tyrosine-protein kinase receptor Ret; Cadherin family member 12; Proto-oncogene c-Ret
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Molecule Type
Protein
Gene Name
RET
Gene ID
5979
Location
chr10:43,077,064-43,130,351[+]
Sequence
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAP
EEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLT
VYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR
PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELV
AVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFD
ADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR
NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFA
QIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAE
LHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR
CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPR
GIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCY
HKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP
RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLK
QVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDH
PDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVY
EEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERL
FNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAA
STPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRA
DGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS
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Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL.
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Uniprot ID
RET_HUMAN
Ensembl ID
ENSG00000165731
HGNC ID
HGNC:9967
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
7 drug(s) in total
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Cabozantinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [2]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
TPC-1 cells Thyroid Homo sapiens (Human) CVCL_6298
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
MTC-TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.C634W (c.1902C>G) in gene RET cause the sensitivity of Cabozantinib by aberration of the drug's therapeutic target
Disease Class: Thyroid gland cancer [2]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
TPC-1 cells Thyroid Homo sapiens (Human) CVCL_6298
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
MTC-TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.M918T (c.2753T>C) in gene RET cause the sensitivity of Cabozantinib by aberration of the drug's therapeutic target
Disease Class: Thyroid gland cancer [3]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
In Vivo Model Female nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Kinase inhibition assay
Mechanism Description The missense mutation p.C634W (c.1902C>G) in gene RET cause the sensitivity of Cabozantinib by unusual activation of pro-survival pathway
Disease Class: Thyroid gland cancer [4]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
Intedanib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Intedanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Intedanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Lenvatinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Lenvatinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Lenvatinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Thyroid gland cancer [5]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Lenvatinib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model FTC-133 cells Thyroid Homo sapiens (Human) CVCL_1219
8305C cells Thyroid Homo sapiens (Human) CVCL_1053
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
TCO-1 cells Lnguinal lymph node Homo sapiens (Human) CVCL_3179
RO82-W-1 cells Thyroid Homo sapiens (Human) CVCL_0582/CVCL_1663
Nthy-ori 3-1 cells N.A. Homo sapiens (Human) CVCL_2659
K1 cells Thyroid Homo sapiens (Human) CVCL_2537
HTC-C3 cells Pleural effusion Homo sapiens (Human) CVCL_2273
FTC-238 cells Lung Homo sapiens (Human) CVCL_2447
FTC-236 cells Cervical lymph node Homo sapiens (Human) CVCL_2446
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; ICH assay
Experiment for
Drug Resistance		 MSA assay; WST-8 assay
Pralsetinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Non-small cell lung cancer [6]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Resistant Drug Pralsetinib
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
Experiment for
Drug Resistance		 Cell-free DNAs (cfDNAs) analysis
Mechanism Description Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.
Disease Class: Advanced RET-altered thyroid cancer [6]
Resistant Disease Advanced RET-altered thyroid cancer [ICD-11: 2D10.Y]
 Disease Info 
Resistant Drug Pralsetinib
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
Experiment for
Drug Resistance		 Cell-free DNAs (cfDNAs) analysis
Mechanism Description Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [7]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Pralsetinib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TPC-1 cells Thyroid Homo sapiens (Human) CVCL_6298
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
LC2/ad cells Pleural effusion Homo sapiens (Human) CVCL_1373
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Promega assay
Disease Class: Thyroid gland cancer [7]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Pralsetinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TPC-1 cells Thyroid Homo sapiens (Human) CVCL_6298
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
LC2/ad cells Pleural effusion Homo sapiens (Human) CVCL_1373
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Promega assay
Regorafenib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [8]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Regorafenib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HUVEC cells Endothelium Homo sapiens (Human) N.A.
HAoSMC cells N.A. . N.A.
In Vivo Model Female athymic NCr nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 CellTitre-Glo assay
Mechanism Description The missense mutation p.C634W (c.1902C>G) in gene RET cause the sensitivity of Regorafenib by unusual activation of pro-survival pathway
Selpercatinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Non-small cell lung cancer [6]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Resistant Drug Selpercatinib
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
Experiment for
Drug Resistance		 Cell-free DNAs (cfDNAs) analysis
Mechanism Description Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.
Disease Class: Advanced RET-altered thyroid cancer [6]
Resistant Disease Advanced RET-altered thyroid cancer [ICD-11: 2D10.Y]
 Disease Info 
Resistant Drug Selpercatinib
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
Experiment for
Drug Resistance		 Cell-free DNAs (cfDNAs) analysis
Mechanism Description Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Lung adenocarcinoma [9]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Selpercatinib
 Drug Info 
Molecule Alteration Other
.
Experimental Note Identified from the Human Clinical Data
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [10]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Selpercatinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
In Vivo Model mouse PDX model Mus musculus
Mechanism Description LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations.
Disease Class: Solid tumour/cancer [10]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Selpercatinib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
In Vivo Model mouse PDX model Mus musculus
Mechanism Description LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations.
Vandetanib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Disease Class: Multiple endocrine neoplasia [1]
Resistant Disease Multiple endocrine neoplasia [ICD-11: 2F7A.0]
 Disease Info 
Resistant Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T
Experimental Note Identified from the Human Clinical Data
In Vitro Model BaF3 cells Bone Mus musculus (Mouse) CVCL_0161
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 LC50 assay
Mechanism Description M918T is a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B. M918T mutation is located at distant sites away from the TKI binding pocket. IC50s of cabozantinib, lenvatinib, vandetanib and nintedanib in BaF3/KR (M918T) cells were 6.5-fold, 7.5-fold, 4.3-fold and 1.7-fold, respectively, higher than in BaF3/KR cells.
Disease Class: Solid tumour/cancer [11]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.V804M (c.2410G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.V804M (c.2410G>A) in gene RET cause the resistance of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.V804L (c.2410G>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.V804L (c.2410G>C) in gene RET cause the resistance of Vandetanib by aberration of the drug's therapeutic target
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Thyroid gland cancer [12]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Identified from the Human Clinical Data
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.C634R (c.1900T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.C634R (c.1900T>C) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.E768D (c.2304G>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.E768D (c.2304G>C) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.L790F (c.2370G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.L790F (c.2370G>T) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.Y791F (c.2372A>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.Y791F (c.2372A>T) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.A883F (c.2647_2648delGCinsTT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.A883F (c.2647_2648delGCinsTT) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.S891A (c.2671T>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.S891A (c.2671T>G) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [11]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Growth curves and transformation assay
Mechanism Description The missense mutation p.M918T (c.2753T>C) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target
Disease Class: Thyroid gland cancer [12]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 PCR
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Lung adenocarcinoma [13]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Vandetanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1271 cells Lung Homo sapiens (Human) CVCL_1716
H1048 cells Pleural effusion Homo sapiens (Human) CVCL_1453
Experiment for
Molecule Alteration		 Western blotting analysis; Sanger sequencing; qPCR
Experiment for
Drug Resistance		 MTT assay
Clinical Trial Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
AZD1480
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [14]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug AZD1480
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model TPC-1 cells Thyroid Homo sapiens (Human) CVCL_6298
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
K1 cells Thyroid Homo sapiens (Human) CVCL_2537
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 TUNEL assay
Mechanism Description The missense mutation p.M918T (c.2753T>C) in gene RET cause the sensitivity of AZD1480 by unusual activation of pro-survival pathway
Disease Class: Thyroid gland cancer [14]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug AZD1480
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model TPC-1 cells Thyroid Homo sapiens (Human) CVCL_6298
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
K1 cells Thyroid Homo sapiens (Human) CVCL_2537
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 TUNEL assay
Mechanism Description The missense mutation p.C634W (c.1902C>G) in gene RET cause the sensitivity of AZD1480 by unusual activation of pro-survival pathway
Agerafenib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [15]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug Agerafenib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ERK signaling pathway Inhibition hsa04210
AKT signaling pathway Inhibition hsa04151
In Vitro Model LC-2/ad cells Lung Homo sapiens (Human) CVCL_1373
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Phospho-protein profiling assay
Experiment for
Drug Resistance		 CellTiter-Glo assay
Mechanism Description RXDX-105 inhibited wild-type RET, CCDC6-RET, NCOA4-RET, PRKAR1A-RET, and RET M918T with low to subnanomolar activity while sparing VEGFR2/KDR and VEGFR1/FLT. RXDX-105 treatment resulted in dose-dependent inhibition of proliferation of CCDC6-RET-rearranged and RET C634W-mutant cell lines and inhibition of downstream signaling pathways. Significant tumor growth inhibition in CCDC6-RET, NCOA4-RET, and KIF5B-RET-containing xenografts was observed, with the concomitant inhibition of p-ERK, p-AKT, and p-PLC gamma.
Discontinued Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Motesanib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Thyroid gland cancer [16]
Resistant Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Resistant Drug Motesanib
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Medullary thyroid cancer tissue Pleural effusion Homo sapiens (Human) CVCL_A656
Mechanism Description The missense mutation p.M918T (c.2753T>C) in gene RET cause the resistance of Motesanib by unusual activation of pro-survival pathway
Disease Class: Thyroid gland cancer [16]
Resistant Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Resistant Drug Motesanib
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Medullary thyroid cancer tissue Pleural effusion Homo sapiens (Human) CVCL_A656
Mechanism Description The missense mutation p.C634W (c.1902C>G) in gene RET cause the resistance of Motesanib by unusual activation of pro-survival pathway
Preclinical Drug(s)
4 drug(s) in total
Click to Show/Hide the Full List of Drugs
ALW-II-41-27
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Thyroid gland cancer [17]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug ALW-II-41-27
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Solid tumour/cancer [17]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ALW-II-41-27
 Drug Info 
Molecule Alteration Missense mutation
p.C634Y (c.1901G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Solid tumour/cancer [17]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ALW-II-41-27
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Thyroid gland cancer [17]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug ALW-II-41-27
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
HG-6-63-01
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [17]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug HG-6-63-01
 Drug Info 
Molecule Alteration Missense mutation
p.C634Y (c.1901G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Solid tumour/cancer [17]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug HG-6-63-01
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Thyroid gland cancer [17]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug HG-6-63-01
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Thyroid gland cancer [17]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug HG-6-63-01
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
PZ-1
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [18]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug PZ-1
 Drug Info 
Molecule Alteration Missense mutation
p.V804M (c.2410G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) N.A.
In Vivo Model Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Microfluidic separation based assay
Disease Class: Solid tumour/cancer [18]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug PZ-1
 Drug Info 
Molecule Alteration Missense mutation
p.V804L (c.2410G>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) N.A.
In Vivo Model Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Microfluidic separation based assay
Disease Class: Solid tumour/cancer [18]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug PZ-1
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) N.A.
In Vivo Model Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Microfluidic separation based assay
XMD15-44
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Thyroid gland cancer [17]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug XMD15-44
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Solid tumour/cancer [17]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug XMD15-44
 Drug Info 
Molecule Alteration Missense mutation
p.C634Y (c.1901G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Solid tumour/cancer [17]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug XMD15-44
 Drug Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease Class: Thyroid gland cancer [17]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Sensitive Drug XMD15-44
 Drug Info 
Molecule Alteration Missense mutation
p.C634W (c.1902C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/V804L cells N.A. Mus musculus (Mouse) CVCL_XZ25
RET/S891A cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/M918T cells N.A. Homo sapiens (Human) N.A.
RET/L790F cells N.A. Homo sapiens (Human) N.A.
RET/E768D cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/C634R cells N.A. Homo sapiens (Human) N.A.
RET/A883F cells N.A. Homo sapiens (Human) N.A.
MZ-CRC-1 cells Pleural effusion Homo sapiens (Human) CVCL_A656
RET/V804M cells Bone marrow Mus musculus (Mouse) CVCL_XZ26
RET/E768D cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell counting assay
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Click to Show/Hide the Resistance Disease of This Class
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Lung
The Specified Disease Lung cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 3.31E-11; Fold-change: 2.66E-02; Z-score: 1.12E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 2.13E-05; Fold-change: -1.67E-02; Z-score: -4.65E-02
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Thyroid cancer [ICD-11: 2D10]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Thyroid
The Specified Disease Thyroid cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.04E-09; Fold-change: 9.40E-02; Z-score: 2.29E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 2.49E-04; Fold-change: 6.98E-02; Z-score: 1.46E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Tissue-specific Molecule Abundances in Healthy Individuals
Click to Show/Hide the Molecule Abundances
Download the Tissue-Specific Variation(s) Profile
References
Ref 1 Drug resistance profiles of mutations in the RET kinase domain .Br J Pharmacol. 2018 Sep;175(17):3504-3515. doi: 10.1111/bph.14395. Epub 2018 Jul 19. 10.1111/bph.14395
Ref 2 The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cellsJ Clin Endocrinol Metab. 2011 Jun;96(6):E991-5. doi: 10.1210/jc.2010-2381. Epub 2011 Apr 6.
Ref 3 In vitro and in vivo activity of cabozantinib (XL184), an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancerThyroid. 2013 Dec;23(12):1569-77. doi: 10.1089/thy.2013.0137. Epub 2013 Sep 17.
Ref 4 Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancerCancer. 2016 Dec 15;122(24):3856-3864. doi: 10.1002/cncr.30252. Epub 2016 Aug 15.
Ref 5 Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer modelsJ Thyroid Res. 2014;2014:638747. doi: 10.1155/2014/638747. Epub 2014 Sep 10.
Ref 6 Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations .Ann Oncol. 2021 Feb;32(2):261-268. doi: 10.1016/j.annonc.2020.10.599. Epub 2020 Nov 5. 10.1016/j.annonc.2020.10.599
Ref 7 Precision Targeted Therapy with BLU-667 for RET-Driven CancersCancer Discov. 2018 Jul;8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15.
Ref 8 Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activityInt J Cancer. 2011 Jul 1;129(1):245-55. doi: 10.1002/ijc.25864. Epub 2011 Apr 22.
Ref 9 Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung CancerN Engl J Med. 2020 Aug 27;383(9):813-824. doi: 10.1056/NEJMoa2005653.
Ref 10 Selective RET kinase inhibition for patients with RET-altered cancersAnn Oncol. 2018 Aug 1;29(8):1869-1876. doi: 10.1093/annonc/mdy137.
Ref 11 Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitorsOncogene. 2004 Aug 12;23(36):6056-63. doi: 10.1038/sj.onc.1207810.
Ref 12 Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trialJ Clin Oncol. 2012 Jan 10;30(2):134-41. doi: 10.1200/JCO.2011.35.5040. Epub 2011 Oct 24.
Ref 13 RET mutation and expression in small-cell lung cancerJ Thorac Oncol. 2014 Sep;9(9):1316-23. doi: 10.1097/JTO.0000000000000234.
Ref 14 AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell linesPLoS One. 2012;7(10):e46869. doi: 10.1371/journal.pone.0046869. Epub 2012 Oct 2.
Ref 15 Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or MutationsClin Cancer Res. 2017 Jun 15;23(12):2981-2990. doi: 10.1158/1078-0432.CCR-16-1887. Epub 2016 Dec 23.
Ref 16 Anti-tumor activity of motesanib in a medullary thyroid cancer modelJ Endocrinol Invest. 2012 Feb;35(2):181-90. doi: 10.3275/7609. Epub 2011 Mar 21.
Ref 17 Identification of Novel Small Molecule Inhibitors of Oncogenic RET KinasePLoS One. 2015 Jun 5;10(6):e0128364. doi: 10.1371/journal.pone.0128364. eCollection 2015.
Ref 18 Fragment-Based Discovery of a Dual pan-RET/VEGFR2 Kinase Inhibitor Optimized for Single-Agent PolypharmacologyAngew Chem Int Ed Engl. 2015 Jul 20;54(30):8717-21. doi: 10.1002/anie.201501104. Epub 2015 Jun 30.

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