BLU-9931

Fibroblast growth factor receptor 4 (FGFR4) is the receptor for fibroblast growth factor 19 (FGF19), which is a tightly controlled hormone that regulates bile acid synthesis and hepatocyte proliferation in the normal liver. Aberrant signaling through the FGFR4/FGF19 signaling complex has been implicated in hepatocellular carcinoma (HCC). BLU-9931 is a small molecule inhibitor of FGFR4 (IC50 = 3 nM) that is selective for FGFR4 over other FGFR family members (IC50s = 591, 493, and 150 nM for FGFR1, 2, and 3, respectively) and an extensive panel of additional kinases (selectivity score for BLU-9931 at 3 µM is 0.005). It inhibits proliferation of HCC cell lines with an activated FGFR4 signaling pathway (EC50s = 0.02-0.11 µM) and demonstrates antitumor activity when administered orally at 100 mg/kg to mice bearing HCC xenografts that overexpresses FGF19 due to amplification or to mice bearing liver tumor xenografts that overexpresses FGF19 mRNA but lack FGF19 amplification.Formal Name: N-[2-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]-2-propenamide. CAS Number: 1538604-68-0. Molecular Formula: C26H22Cl2N4O3. Formula Weight: 509.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS(pH 7.2) (1:2): 0.3 mg/ml, Ethanol: 0.2 mg/ml. lambdamax: 251 nm. SMILES: ClC1=C(C2=CC(C=NC(NC3=C(C)C=CC=C3NC(C=C)=O)=N4)=C4C=C2)C(Cl)=C(OC)C=C1OC. InChi Code: InChI=1S/C26H22Cl2N4O3/c1-5-21(33)30-18-8-6-7-14(2)25(18)32-26-29-13-16-11-15(9-10-17(16)31-26)22-23(27)19(34-3)12-20(35-4)24(22)28/h5-13H,1H2,2-4H3,(H,30,33)(H,29,31,32). InChi Key: TXEBNKKOLVBTFK-UHFFFAOYSA-N.