Home Protein Tyrosine Kinase FGFR inhibitor H3B-6527 For research use only.

H3B-6527

H3B-6527 is a highly selective covalent FGFR4 inhibitor with an IC50 value of <1.2 nM and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nM respectively).

H3B-6527 Chemical Structure

H3B-6527 Chemical Structure

CAS No. 1702259-66-2

Purity & Quality Control

H3B-6527 Related Products

Signaling Pathway

FGFR Signaling Pathways

FGFR Signaling Pathway

Biological Activity

Description H3B-6527 is a highly selective covalent FGFR4 inhibitor with an IC50 value of <1.2 nM and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nM respectively).
Targets
FGFR4 [1]
(Cell-free assay)
<1.2 nM
In vitro
In vitro

H3B-6527 shows robust inhibition of the target kinase FGFR4 with an IC50 value of <1.2 nmol/L and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nmol/L respectively). TAOK2, JNK2, and CSF1R are also less sensitive to H3B-6527 treatment with IC50 values of 690, >10,000, and >10,000 nmol/L, respectively. H3B-6527 inhibits FGFR4 signaling, proliferation, and leads to apoptosis in a HCC cell line (Hepatocellular carcinoma). 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. H3B-6527 has the selectivity and the selective dependence on FGFR4 across cancer types[1].
Cell Research Cell lines Hep3B cells
Concentrations 100 and 300 nmol/L
Incubation Time 0.5, 1, 2, 4, 8, and 24 hours
Method

Hep3B cells are treated with H3B-6527 at 100 and 300 nmol/L for 0.5, 1, 2, 4, 8, and 24 hours and pERK1/2 levels are measured.
In Vivo
In vivo

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). The H3B-6527 pharmacodynamic response as measured by CYP7A1 mRNA and pERK1/2 protein levels is dose dependent, with higher doses leading to sustained responses. 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.
Animal Research Animal Models BALB/c nu/nu female mice
Dosages 30, 100, and 300 mg/kg
Administration orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03424577 Completed
Healthy Participants
Eisai Inc.|H3 Biomedicine Inc.
 December 27 2017 Phase 1
NCT02834780 Completed
Advanced Hepatocellular Carcinoma|Hepatocellular Carcinoma|Liver Cancer|Liver Neoplasms|Hepatic Cancer|Hepatic Carcinoma
H3 Biomedicine Inc.|Eisai Inc.
 December 28 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 629.54 Formula

C29H34Cl2N8O4
CAS No. 1702259-66-2 SDF Download H3B-6527 SDF
Smiles CCN1CCN(CC1)C2=CC(=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl)NC(=O)C=C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 50 mg/mL ( (79.42 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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