H3B-6527

Investigational

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 Search

SMILES

CCN1CCN(CC1)C2=CC=C(NC3=CC(=NC=N3)N(C)C(=O)NC4=C(Cl)C(OC)=CC(OC)=C4Cl)C(NC(=O)C=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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29247039

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

Targets

Primary Target	Pharmacology	Potency
Fibroblast growth factor receptor 4 16 Target ID: CHEMBL3973 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29247039	Inhibitor 8504	1.2 nM [IC50]
Fibroblast growth factor receptor 1 46 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29247039	Inhibitor 8504
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29247039	Inhibitor 8504
Fibroblast growth factor receptor 2 25 Target ID: CHEMBL4142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29247039	Inhibitor 8504

C_max

Value	Dose	Co-administered	Analyte	Population
225 ng/mL CLINICAL TRIAL https://www.clinicaltrials.gov/study/NCT02834780	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		H3B-6527 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
182 ng/mL CLINICAL TRIAL https://www.clinicaltrials.gov/study/NCT02834780	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		H3B-6527 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
850 ng × h/mL CLINICAL TRIAL https://www.clinicaltrials.gov/study/NCT02834780	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		H3B-6527 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1115 ng × h/mL CLINICAL TRIAL https://www.clinicaltrials.gov/study/NCT02834780	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		H3B-6527 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.5 h EXPERIMENT https://doi.org/10.1200/JCO.2021.39.15_suppl.4090	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		H3B-6527 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

PubMed

Title	Date	PubMed
H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma.	2017 Dec 15	29247039

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:41:50 GMT 2025` Edited by `admin` on `Mon Mar 31 23:41:50 GMT 2025`
Record UNII	4HTE364XIK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

H3B-6527

Code

English

H3B 6527 [WHO-DD]

Preferred Name

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

Classification Tree Code System Code

EU-Orphan Drug

EU/3/17/1902