U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C29H34Cl2N8O4
Molecular Weight 629.537
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of H3B-6527

SMILES

CCN1CCN(CC1)C2=CC(NC(=O)C=C)=C(NC3=NC=NC(=C3)N(C)C(=O)NC4=C(Cl)C(OC)=CC(OC)=C4Cl)C=C2

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

Molecular Formula C29H34Cl2N8O4
Molecular Weight 629.537
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Substance Class Chemical
Created
by admin
on Thu Jul 06 16:48:15 UTC 2023
Edited
by admin
on Thu Jul 06 16:48:15 UTC 2023
Record UNII
4HTE364XIK
Record Status Validated (UNII)
Record Version
  • Download
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 Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
FDA ORPHAN DRUG 597717
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C128862
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
PRIMARY
SMS_ID
100000177354
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
PRIMARY
CAS
1702259-66-2
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
PRIMARY
FDA UNII
4HTE364XIK
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
PRIMARY
PUBCHEM
118029202
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
PRIMARY
DRUG BANK
DB15169
Created by admin on Thu Jul 06 16:48:15 UTC 2023 , Edited by admin on Thu Jul 06 16:48:15 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY