H3B-6527 Chemical Properties

Boiling point:

832.1±65.0 °C(Predicted)

Density 

1.373±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:50.0(Max Conc. mg/mL);79.42(Max Conc. mM)

form 

A solid

pka

11.00±0.70(Predicted)

color 

White to khaki

H3B-6527 Usage And Synthesis

Biological Activity

H3B-6527 is a highly selective covalent FGFR4 inhibitor with IC50 < 1.2 nM, with >250-fold selectivity for FGFR4 over FGFR1-3 (IC50s of 320, 1290 and 1290 for FGFR1-3, respectively) 1060 nM).

in vitro

H3B-6527 has a strong inhibitory effect on FGFR4 with IC50 less than 1.2 nM. TAOK2, JNK2 and CSF1R were less sensitive to H3B-6527 treatment with IC50s of 690, >10000 and >10000 nmol/L, respectively. Treatment of Hep3B cells with H3B-6527 resulted in a concentration-dependent activation of caspase-3/7. It inhibits FGFR4 signaling, inhibits proliferation, and causes apoptosis in HCC cells.

in vivo

In a mouse model of Hep3B hepatocarcinoma xenografts, H3B-6527 had dose-proportional plasma exposure (greater than tumor exposure; doses tested were 30, 100, and 300 mg/kg). The pharmacodynamic response of H3B-6527 was detected, and it was found that CYP7A1 mRNA and pERK1/2 protein levels showed a concentration-dependent response, and higher concentrations would lead to a more durable response. In both subcutaneous Hep3B xenograft models and orthotopic xenograft models, oral administration of it (twice a day) significantly inhibited the growth of xenografts. Palbociclib enhanced the potency of it and promoted tumor regression in the JHH-7 model, whereas it single-agent administration only caused tumor growth arrest.

H3B-6527(1702259-66-2)Related Product Information

• 3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide
• 2-[[(2E)-3-(2-NAPHTHALENYL)-1-OXO-2-BUTEN-1-YL]AMINO]BENZOIC ACID
• Upadacitinib
• Q-VD-OPh hydrate
• N-(2-(4'-cyanobiphenyl-4-yl)propyl)propane-2-sulfonaMide
• 1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one
• Senexin B
• 2-(2-((4-bromophenyl)amino)-2-oxoethoxy)-N-(2-(methyl(phenyl)amino)-2-oxoethyl)benzamide
• (S)-4-(4-((2-(3,5-diMethylphenyl)pyrrolidin-1-yl)Methyl)phenoxy)-3-fluorobenzaMide
• BMS-986205
• Budiodarone tartrate
• COH-29