Molecule Information

General Information of the Molecule (ID: Mol01836)

• Name: Fibroblast growth factor receptor 3 (FGFR3) ,Homo sapiens
• Synonyms: Fibroblast growth factor receptor 3; FGFR-3; CD antigen CD333; JTK4
• Molecule Type: Protein
• Gene Name: FGFR3
• Gene ID: 2261
• Location: chr4:1,793,293-1,808,872[+]
• Sequence:
  MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELS
  CPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCH
  FSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG
  NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQT
  YTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGP
  DGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAE
  EELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLK
  RQVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARLTLGKPLGE
  GCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIIN
  LLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQ
  VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKW
  MAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCT
  HDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSS
  SSSGDDSVFAHDLLPPAPPSSGGSRT
• Function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.
• Uniprot ID: FGFR3_HUMAN
• Ensembl ID: ENSG00000068078
• HGNC ID: HGNC:3690

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

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Erdafitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Transitional cell carcinoma [1]

• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.S371C (c.1111A>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.G380R (c.1138G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Synonymous; p.K650K (c.1950G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Transitional cell carcinoma [1]

• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Transitional cell carcinoma [1]

• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Transitional cell carcinoma [1]

• Sensitive Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Disease Class: Bladder cancer [1]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Erdafitinib
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Infigratinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.V555L (c.1663G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555L (c.1663G>C) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Transitional cell carcinoma [5]

• Resistant Disease: Transitional cell carcinoma [ICD-11: 2C9Z.0]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Experimental Note: Identified from the Human Clinical Data

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Head and neck squamous cell carcinoma [6]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.S131L (c.392C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: HN cells; Cervical lymph node; Homo sapiens (Human); CVCL_1283
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: 584-A2 cells; Larynx; Homo sapiens (Human); CVCL_V278
• Experiment for Molecule Alteration: Immunohistochemical staining assay; qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: In vitro, FGFR3 overexpression led to increased proliferation, whereas migration was not altered. Moreover, FGFR3-overexpressing cells were more sensitive to BGJ398. Cells overexpressing FGFR3 mutant versions showed increased proliferation compared to wild-type FGFR3 under serum-reduced conditions and were largely as sensitive as the wild-type protein to BGJ398.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.S371C (c.1111A>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.G380R (c.1138G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Solid tumour/cancer [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.R248C (c.742C>T) in gene FGFR3 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Synonymous; p.K650K (c.1950G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Solid tumour/cancer [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Urinary system cancer [9]

• Sensitive Disease: Urinary system cancer [ICD-11: 2C95.Y]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: BaF3 cells; Bone; Mus musculus (Mouse); CVCL_0161
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: UMUC14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: NCI-H2444 cells; Lung; Homo sapiens (Human); CVCL_1552
• In Vitro Model: NCI-H1581 cells; Lung; Homo sapiens (Human); CVCL_1479
• In Vitro Model: MFM-223 cells; Pleural effusion; Homo sapiens (Human); CVCL_1408
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Mechanism Description: c-Myc functioned as the key downstream effector that preceded FGFR-MEK/ERK signaling in FGFR aberrant cancer. Disruption of c-Myc overrode the cell proliferation driven by constitutively active FGFR. FGFR inhibition in FGFR-addicted cancer facilitated c-Myc degradation via phosphorylating c-Myc at threonine 58. Ectopic expression of undegradable c-Myc mutant conferred resistance to FGFR inhibition both in vitro and in vivo. c-Myc level alteration stringently determined the response to FGFR inhibitors, as demonstrated in FGFR-responsive cancer subset, as well as cancers bearing acquired or de novo resistance to FGFR inhibition.

Nivolumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Primary pulmonary lymphoepithelioma-like carcinoma [10]

• Resistant Disease: Primary pulmonary lymphoepithelioma-like carcinoma [ICD-11: 2D4Y.Z]
• Resistant Drug: Nivolumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• Mechanism Description: Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

Clinical Trial Drug(s) 6 drug(s) in total

Cediranib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Bladder cancer [11]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Resistant Drug: Cediranib
• Molecule Alteration: Missense mutation; p.Y375C (c.1124A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.Y375C (c.1124A>G) in gene FGFR3 cause the resistance of Cediranib by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Bladder cancer [11]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Cediranib
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway

Derazantinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Bladder cancer [12]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Derazantinib
• Molecule Alteration: Missense mutation; p.K652E (c.1954A>G)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: SW780 cells; Bladder; Homo sapiens (Human); CVCL_1728
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: RT-112 cells; Urinary bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: MFM-223 cells; Pleural effusion; Homo sapiens (Human); CVCL_1408
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: COS-1 cells; Kidney; Chlorocebus aethiops (Green monkey); CVCL_0223
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.

AZD-4547

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of AZD-4547 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [3]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of AZD-4547 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [3]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Synonymous; p.K650K (c.1950G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.S371C (c.1111A>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.G380R (c.1138G>A)
• Experimental Note: Identified from the Human Clinical Data

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Urinary system cancer [9]

• Sensitive Disease: Urinary system cancer [ICD-11: 2C95.Y]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: BaF3 cells; Bone; Mus musculus (Mouse); CVCL_0161
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: UMUC14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: NCI-H2444 cells; Lung; Homo sapiens (Human); CVCL_1552
• In Vitro Model: NCI-H1581 cells; Lung; Homo sapiens (Human); CVCL_1479
• In Vitro Model: MFM-223 cells; Pleural effusion; Homo sapiens (Human); CVCL_1408
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Mechanism Description: c-Myc functioned as the key downstream effector that preceded FGFR-MEK/ERK signaling in FGFR aberrant cancer. Disruption of c-Myc overrode the cell proliferation driven by constitutively active FGFR. FGFR inhibition in FGFR-addicted cancer facilitated c-Myc degradation via phosphorylating c-Myc at threonine 58. Ectopic expression of undegradable c-Myc mutant conferred resistance to FGFR inhibition both in vitro and in vivo. c-Myc level alteration stringently determined the response to FGFR inhibitors, as demonstrated in FGFR-responsive cancer subset, as well as cancers bearing acquired or de novo resistance to FGFR inhibition.

DEBIO-1347

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of DEBIO-1347 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of DEBIO-1347 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of DEBIO-1347 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bladder cancer [13]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Synonymous; p.K650K (c.1950G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.G370C (c.1108G>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.S371C (c.1111A>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Bladder cancer [2]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.G380R (c.1138G>A)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Myeloproliferative neoplasm [13]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Myeloproliferative neoplasm [13]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.F386L (c.1156T>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Myeloproliferative neoplasm [13]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Bladder cancer [7]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Solid tumour/cancer [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of DEBIO-1347 by aberration of the drug's therapeutic target

LY-2874455

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: LY-2874455
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of LY-2874455 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: LY-2874455
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: LY-2874455
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: LY-2874455
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

PRN1371

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [14]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PRN1371
• Molecule Alteration: Missense mutation; p.K650M (c.1949A>T)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Preclinical Drug(s) 4 drug(s) in total

E7090

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Multiple myeloma [15]

• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Sensitive Drug: E7090
• Molecule Alteration: Missense mutation; p.Y373C (c.1118A>G)
• Experimental Note: Identified from the Human Clinical Data

FIIN-2

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: FIIN-2
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of FIIN-2 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: FIIN-2
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of FIIN-2 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: FIIN-2
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of FIIN-2 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: FIIN-2
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the sensitivity of FIIN-2 by aberration of the drug's therapeutic target

R3Mab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [16]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: R3Mab
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Disease Class: Bladder cancer [16]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: R3Mab
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: R3Mab
• Molecule Alteration: Missense mutation; p.G372C (c.1114G>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.G372C (c.1114G>T) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: R3Mab
• Molecule Alteration: Missense mutation; p.Y375C (c.1124A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.Y375C (c.1124A>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: R3Mab
• Molecule Alteration: Missense mutation; p.K652E (c.1954A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.K652E (c.1954A>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: R3Mab
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.R248C (c.742C>T) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

SU5402

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Myeloproliferative neoplasm [17]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Sensitive Drug: SU5402
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Blood vessel; .
• Experiment for Molecule Alteration: Mass spectrum assay
• Experiment for Drug Resistance: CellTiter 96 aqueous one solution cell proliferation assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of SU5402 by aberration of the drug's therapeutic target

Investigative Drug(s) 1 drug(s) in total

PD98059

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PD98059
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: COS-1 cells; Kidney; Chlorocebus aethiops (Green monkey); CVCL_0223
• Experiment for Molecule Alteration: Immunoprecipitation and immunoblot analysis
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of PD98059 by unusual activation of pro-survival pathway

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Multiple myeloma [ICD-11: 2A83]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Multiple myeloma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.39E-16; Fold-change: 3.84E-02; Z-score: 3.90E-01
• The Studied Tissue: Peripheral blood
• The Specified Disease: Multiple myeloma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.19E-01; Fold-change: -4.66E-02; Z-score: -5.74E-01

Bladder cancer [ICD-11: 2C94]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bladder tissue
• The Specified Disease: Bladder cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.53E-02; Fold-change: -6.43E-01; Z-score: -9.59E-01

References

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• Ref 15: E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical ModelsMol Cancer Ther. 2016 Nov;15(11):2630-2639. doi: 10.1158/1535-7163.MCT-16-0261. Epub 2016 Aug 17.
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