H3B-6527

Catalog No.S8675 Batch:S867501

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Technical Data

Formula

C29H34Cl2N8O4
Molecular Weight 629.54 CAS No. 1702259-66-2
Solubility (25°C)* In vitro DMSO 50 mg/mL (79.42 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 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].
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. Palbociclib can enhance H3B-6527 efficacy and promote tumor regression in JHH-7 model where H3B-6527 as a single agent can only lead to tumor stasis[1].

Protocol (from reference)

Cell Assay:

[1]
  • 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.
Animal Study:

[1]
  • Animal Models

    BALB/c nu/nu female mice

  • Dosages

    30, 100, and 300 mg/kg

  • Administration

    orally

Customer Product Validation

Data from [Data independently produced by , , Thorac Cancer, 2018, 9(12):1687-1698]

Selleck's H3B-6527 has been cited by 11 publications

Compartmentalization and synergy of osteoblasts drive bone formation in the regenerating fin [ iScience, 2024, 27(2):108841] PubMed: 38318374
FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling [ J Exp Clin Cancer Res, 2023, 42(1):96] PubMed: 37085881
Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary KIT Mutations [ Cancers (Basel), 2023, 15(22)5354] PubMed: 38001614
Indoxyl sulfate induces left ventricular hypertrophy via the AhR-FGF23-FGFR4 signaling pathway [ Front Cardiovasc Med, 2023, 10:990422] PubMed: 36895836
Indoxyl sulfate induces left ventricular hypertrophy via the AhR-FGF23-FGFR4 signaling pathway [ Front Cardiovasc Med, 2023, 10:990422] PubMed: 36895836
BCL-XL inhibition induces an FGFR4-mediated rescue response in colorectal cancer [ Cell Rep, 2022, 38(7):110374] PubMed: 35172148
Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma [ Br J Cancer, 2022, 10.1038/s41416-022-01973-6] PubMed: 36097178
FGF15 promotes hepatic NPC1L1 degradation in lithogenic diet-fed mice [ Lipids Health Dis, 2022, 21(1):97] PubMed: 36209166
FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis [ J Exp Clin Cancer Res, 2021, 40(1):93] PubMed: 33691750
Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer [ NPJ Precis Oncol, 2021, 5(1):66] PubMed: 34272467

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.