H3B-6527

製品コードS8675 バッチS867501

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C29H34Cl2N8O4
分子量 629.54 CAS No. 1702259-66-2
Solubility (25°C)* 体外 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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).
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].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Hep3B cells
濃度 100 and 300 nmol/L
反応時間 0.5, 1, 2, 4, 8, and 24 hours
実験の流れ

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.
動物実験 動物モデル BALB/c nu/nu female mice
投薬量 30, 100, and 300 mg/kg
投与方法 orally

カスタマーフィードバック

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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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人間や獣医の診断であるか治療的な使用のためにでない。

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