H3B-6527

H3B-6527 is an inhibitor of FGF receptor 4 (FGFR4, IC50 = 50s = 320, 1,290, and 1,060 nM, respectively), as well as TAOK2, JNK2, and CSF1R (IC50s = 690, >10,000, and >10,000 nM, respectively). H3B-6527 increases the expression of the cytochrome P450 (CYP) isoform CYP7A1 and decreases phosphorylation of ERK1/2 in Hep3B hepatocellular carcinoma (HCC) cells in a concentration-dependent manner, indicating inhibition of the FGF19-FGFR4 signaling pathway. It also decreases cell growth (GI50 = 25 nM) and increases caspase-3/7 activity in Hep3B HCC cells. H3B-6527 selectively inhibits cell growth in HCC cell lines that express high levels of FGF19 and have high FGF19 protein levels. It reduces tumor growth in a Hep3B HCC mouse xenograft model, when administered at doses of 100 and 300 mg/kg, and in patient-derived xenograft models with high FGF19 expression. H3B-6527, in combination with PD 0332991 (palbociclib, Cay-16273), induces tumor stasis in a JHH-7 mouse xenograft model.Formal Name: N-[2-[[6-[[[(2,6-dichloro-3,5-dimethoxyphenyl)amino]carbonyl]methylamino]-4-pyrimidinyl]amino]-5-(4-ethyl-1-piperazinyl)phenyl]-2-propenamide. CAS Number: 1702259-66-2. Molecular Formula: C29H34Cl2N8O4. Formula Weight: 629.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. SMILES: ClC1=C(NC(N(C2=CC(NC3=C(NC(C=C)=O)C=C(N4CCN(CC)CC4)C=C3)=NC=N2)C)=O)C(Cl)=C(OC)C=C1OC. InChi Code: InChI=1S/C29H34Cl2N8O4/c1-6-25(40)35-20-14-18(39-12-10-38(7-2)11-13-39)8-9-19(20)34-23-16-24(33-17-32-23)37(3)29(41)36-28-26(30)21(42-4)15-22(43-5)27(28)31/h6,8-9,14-17H,1,7,10-13H2,2-5H3,(H,35,40)(H,36,41)(H,32,33,34). InChi Key: MBWRLLRCTIYXDW-UHFFFAOYSA-N.