Pemigatinib

Pemigatinib is an inhibitor of FGFR (IC50s = 0.4, 0.5, and 1 nM for FGFR1, FGFR2, and FGFR3, respectively). It is selective for FGFR1, FGFR2, and FGFR3 over FGFR4 and the kinase insert domain receptor (KDR, IC50s = 30 and 70 nM, respectively), as well as over a panel of 56 tyrosine and serine/threonine kinases at 10 µM. Pemigatinib reduces phosphorylation of FGFR, ERK1/2, and STAT5 in KG-1a acute myeloid leukemia cells in a concentration-dependent manner. It inhibits growth in a panel of cancer cell lines expressing constitutively active FGFR, including lung, bladder, and gastric cancer cells, with GI50 values ranging from 3 to 362 nM. Pemigatinib (0.3 mg/kg per day) reduces tumor growth in KATO III, KG-1, and RT-112 mouse xenograft models.Formal Name: 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-1,3,4,7-tetrahydro-8-(4-morpholinylmethyl)-2H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2-one. CAS Number: 1513857-77-6. Synonyms: INCB054828. Molecular Formula: C24H27F2N5O4. Formula Weight: 487.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 15 mg/ml, DMF:PBS (pH 7.2) (1:2): 0.33 mg/ml, DMSO: 5 mg/ml. lambdamax: 231, 289 nm. SMILES: O=C1N(CC2=CNC3=NC(CN4CCOCC4)=CC3=C2N1CC)C5=C(F)C(OC)=CC(OC)=C5F. InChi Code: 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). InChi Key: HCDMJFOHIXMBOV-UHFFFAOYSA-N.