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Details

Stereochemistry ACHIRAL
Molecular Formula C29H34Cl2N8O4
Molecular Weight 629.5384
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of H3B-6527

SMILES

C=CC(=Nc1cc(ccc1Nc2cc(ncn2)N(C)C(=Nc3c(c(cc(c3Cl)OC)OC)Cl)O)N4CCN(CC)CC4)O

InChI

InChIKey=MBWRLLRCTIYXDW-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
H3B-6527 is a highly selective covalent FGFR4 inhibitor with at least 250-fold selectivity over FGFR1-3. H3B-6527 inhibits FGFR4 signaling, proliferation, and leads to apoptosis in Hepatocellular carcinoma (HCC) cell line. Treatment on Hep3B cells leads to robust activation of caspase-3/7, an apoptotic marker, in a concentration-dependent manner, indicating FGFR4 inhibition by H3B-6527 leads to cell death in HCC cell lines. In the Hep3B human HCC xenograft mouse model, H3B-6527 shows dose-proportional plasma exposures and greater than dose-proportional tumor exposures within the dose range evaluated (30, 100, and 300 mg/kg). Oral treatment of H3B-6527, twice daily, inhibits xenograft growth in a dose-dependent manner in nude mice, with the 300 or 100 mg/kg twice daily, significantly inhibiting tumor growth in both Hep3B subcutaneous and orthotopic xenograft model and causing tumor regressions in the subcutaneous xenograft model.

Approval Year

PubMed

PubMed

TitleDatePubMed
H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma.
2017 Dec 15
Name Type Language
H3B-6527
Code English
2-PROPENAMIDE, N-(2-((6-((((2,6-DICHLORO-3,5-DIMETHOXYPHENYL)AMINO)CARBONYL)METHYLAMINO)-4-PYRIMIDINYL)AMINO)-5-(4-ETHYL-1-PIPERAZINYL)PHENYL)-
Systematic Name English
N-(2-((6-(((2,6-DICHLORO-3,5 DIMETHOXYPHENYL) CARBAMOYL) (METHYL)AMINO)PYRIMIDIN-4-YL)AMINO)-5-(4-ETHYLPIPERAZIN-1-YL)PHENYL)PROP-2-ENAMIDE
Systematic Name English
H3B 6527 [WHO-DD]
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/17/1902
Created by admin on Sat Jun 26 08:24:35 UTC 2021 , Edited by admin on Sat Jun 26 08:24:35 UTC 2021
FDA ORPHAN DRUG 597717
Created by admin on Sat Jun 26 08:24:35 UTC 2021 , Edited by admin on Sat Jun 26 08:24:35 UTC 2021
Code System Code Type Description
CAS
1702259-66-2
Created by admin on Sat Jun 26 08:24:35 UTC 2021 , Edited by admin on Sat Jun 26 08:24:35 UTC 2021
PRIMARY
FDA UNII
4HTE364XIK
Created by admin on Sat Jun 26 08:24:35 UTC 2021 , Edited by admin on Sat Jun 26 08:24:35 UTC 2021
PRIMARY
PUBCHEM
118029202
Created by admin on Sat Jun 26 08:24:35 UTC 2021 , Edited by admin on Sat Jun 26 08:24:35 UTC 2021
PRIMARY
DRUG BANK
DB15169
Created by admin on Sat Jun 26 08:24:35 UTC 2021 , Edited by admin on Sat Jun 26 08:24:35 UTC 2021
PRIMARY