Drug Information

Drug (ID: DG01307) and It's Reported Resistant Information
Name
Pralsetinib
Synonyms
Pralsetinib; BLU-667; 2097132-94-8; Pralsetinib free base; cis-Pralsetinib; Blu667; trans-Pralsetinib; UNII-1WPE73O1WV; 1WPE73O1WV; BLU123244; 2097132-94-8 (free base); 2097132-93-7; N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide; X581238; cis-N-{(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]ethyl}-1-methoxy-4-{4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}cyclohexane-1-carboxamide; Gavreto; Cyclohexanecarboxamide, N-((1S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)-3-pyridinyl)ethyl)-1-methoxy-4-(4-methyl-6-((5-methyl-1H-pyrazol-3-yl)amino)-2-pyrimidinyl)-, cis-; cyclohexanecarboxamide, N-[(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)-3-pyridinyl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]-, cis-; Q4J; Pralsetinib [INN]; Pralsetinib [USAN]; Blu667Blu667; cis-BLU-667; Pralsetinib (USAN/INN); BLU-667 (Pralsetinib); CHEMBL4582651; SCHEMBL18789228; SCHEMBL18789229; SCHEMBL18806610; GTPL10033; BDBM435009; BDBM435010; AMY16875; EX-A1944; EX-A3347; NSC811429; s8716; US10584114, Compound 129; US10584114, Compound 130; WHO 11004; AKOS037648884; BLU-123244; HY-112301A; NSC-811429; BS-15942; HY-112301; CS-0043448; CS-0044766; D11712; X-581238; (cis)-N-((S)-1-(6-(4-Fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4-methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide; BLU-667; trans-N-{(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]ethyl}-1-methoxy-4-{4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}cyclohexane-1-carboxamide; trans-N-{(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]ethyl}-1-methoxy-4-{4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}cyclohexane-1-carboxamide
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Indication
In total 2 Indication(s)
Non-small-cell lung cancer [ICD-11: 2C25]
Approved
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Lung cancer [ICD-11: 2C25]
[1]
Thyroid cancer [ICD-11: 2D10]
[1]
Target Proto-oncogene c-Ret (RET) RET_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C27H32FN9O2
IsoSMILES
CC1=CC(=NN1)NC2=NC(=NC(=C2)C)C3CCC(CC3)(C(=O)N[C@@H](C)C4=CN=C(C=C4)N5C=C(C=N5)F)OC
InChI
1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19 ,27 /m0/s1
InChIKey
GBLBJPZSROAGMF-SIYOEGHHSA-N
PubChem CID
129073603
TTD Drug ID
D0OD2I
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Thyroid cancer [ICD-11: 2D10]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [2]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.M918T (c.2753T>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.64  Å
PDB: 7DUA
Mutant Type Structure Method: X-ray diffraction Resolution: 2.12  Å
PDB: 4CKI
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.93
TM score: 0.95555
Amino acid change:
M918T
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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700
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710
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720
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N
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730
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E
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G
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E
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740
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A
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T
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A
F
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H
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750
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A
A
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Y
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760
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L
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770
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780
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790
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800
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810
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820
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830
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840
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850
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860
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870
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880
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890
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900
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910
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920
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930
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940
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L
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950
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960
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L
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G
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970
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M
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N
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C
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980
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M
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990
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1000
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1010
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Click to Show/Hide the Structure
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 blot analysis
Experiment for
Drug Resistance		 Promega assay
References
Ref 1 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 2 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.

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