Drug Information

Drug (ID: DG01304) and It's Reported Resistant Information

• Name: Pemigatinib
• Synonyms: Pemigatinib; 1513857-77-6; INCB054828; Pemazyre; UNII-Y6BX7BL23K; Y6BX7BL23K; Fgfr inhibitor INCB054828; INCB54828; INCB-54828; INCB-054828; 1513857-77-6 (free base); 3-(2,6-Difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholinomethyl)-1,3,4,6-tetrahydro-2H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2-one; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-[(morpholin-4-yl)methyl]-1,3,4,7-tetrahydro-2Hpyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2-one; Pemazyre (TN); Pemigatinib [INN]; Pemigatinib [USAN]; Pemigatinib [USAN:INN]; Pemigatinib (JAN/USAN/INN); GTPL9767; Pemigatinib (INCB054828); CHEMBL4297522; SCHEMBL15556271; BDBM301310; INCB 54828; EX-A4049; NSC816556; US10131667, Example 126; AT15587; DB15102; INCB054828INCB054828; NSC-816556; AS-78489; example 126 [WO2014007951]; HY-109099; CS-0039499; D11417; A936247; 11-(2,6-difluoro-3,5-dimethoxyphenyl)-13-ethyl-4-(morpholin-4-ylmethyl)-5,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1,3,6,8-tetraen-12-one; 2H-Pyrrolo(3',2':5,6)pyrido(4,3-d)pyrimidin-2-one, 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-1,3,4,7-tetrahydro-8-(4-morpholinylmethyl)-; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3'',2'':5,6]pyrido[4,3-d]pyrimidin-2-one; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2-one; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholinomethyl)-3,4-dihydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one
• Indication:
  In total 3 Indication(s)
  Bladder cancer [ICD-11: 2C94]; Approved; [1]
  Cholangiocarcinoma [ICD-11: 2C12]; Approved; [1]
  Myeloproliferative syndrome [ICD-11: 2A20]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Liver cancer [ICD-11: 2C12]; [1]
• Target: Fibroblast growth factor receptor 1 (FGFR1); FGFR1_HUMAN; [1]
• Target: Fibroblast growth factor receptor 2 (FGFR2); FGFR2_HUMAN; [1]
• Target: Fibroblast growth factor receptor 3 (FGFR3); FGFR3_HUMAN; [1]
• Formula: C24H27F2N5O4
• IsoSMILES: CCN1C2=C3C=C(NC3=NC=C2CN(C1=O)C4=C(C(=CC(=C4F)OC)OC)F)CN5CCOCC5
• InChI: 1S/C24H27F2N5O4/c1-4-30-21-14(11-27-23-16(21)9-15(28-23)13-29-5-7-35-8-6-29)12-31(24(30)32)22-19(25)17(33-2)10-18(34-3)20(22)26/h9-11H,4-8,12-13H2,1-3H3,(H,27,28)
• InChIKey: HCDMJFOHIXMBOV-UHFFFAOYSA-N
• PubChem CID: 86705695
• TTD Drug ID: D0O6UY

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Liver cancer [ICD-11: 2C12]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Function; Inhibition
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genomic profiling assay
• Mechanism Description: The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with FGFR2. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Pemigatinib is a selective, potent, oral, competitive inhibitor of FGFR1, 2, and 3 that inhibits receptor autophosphorylation and subsequent activation of FGF/FGFR-mediated signaling networks, leading to an inhibition of tumor cell growth in FGFR-driven cancers.

References

• Ref 1: Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib .Cancer Discov. 2021 Feb;11(2):326-339. doi: 10.1158/2159-8290.CD-20-0766. Epub 2020 Nov 20. 10.1158/2159-8290.CD-20-0766