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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C29H34Cl2N8O4 |
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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. |
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). |
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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]. |
細胞アッセイ | 細胞株 | Hep3B cells |
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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. |
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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 |
Data from [Data independently produced by , , Thorac Cancer, 2018, 9(12):1687-1698]
Paradoxical cancer cell proliferation after FGFR inhibition through decreased p21 signaling in FGFR1-amplified breast cancer cells [ Breast Cancer Res, 2024, 26(1):54] | PubMed: 38553760 |
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 |
長期の保管のために-20°Cの下で製品を保ってください。
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。