| CAS NO: | 1392429-79-6 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Name: BI 882370 CAS#: 1392429-79-6 Chemical Formula: C28H33F2N7O2S Exact Mass: 569.2385 Molecular Weight: 569.68 | |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Technical Information | Synonym: BI-882370; BI882370; BI 882370. Chemical Name: N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-2,4-difluorophenyl)propane-1-sulfonamide InChi Key: GAIOPWBQKZMUNO-UHFFFAOYSA-N InChi Code: InChI=1S/C15H15FN6O2S2/c1-8-13(25-15(18-2)20-8)12-11(16)7-19-14(22-12)21-9-4-3-5-10(6-9)26(17,23)24/h3-7H,1-2H3,(H,18,20)(H2,17,23,24)(H,19,21,22) SMILES Code: O=S(C1=CC=CC(NC2=NC=C(F)C(C3=C(C)N=C(NC)S3)=N2)=C1)(N)=O |
| Target | IC50s for Braf: 0.6 nM (IC50); c-Raf: 0.8 nM; BRafV600E: 0.4 nM |
|---|---|
| In Vitro | BI-882370 (0.9-6000 nM; 3 days) inhibits the BRAF-mutant human melanoma and colorectal cancer cells proliferation with a EC50 range of 1-10 nM[1]. BI-882370 (0.1-100 nM, 0.1-3000 nM; 2 hours, 24 hours) results in a reduction of p-MEK1/2, p-ERK1/2 and cyclin D1/D2 expression in BRAFV600E-mutant A375 cells; induces p-MEK1/2 and enhances p-ERK1/2 , cyclins D1/D2 or Kip1/p27 is not affected in BRO cells[1]. Cell Proliferation Assay[1] Cell Line: BRAF-mutant and WT melanoma cell lines (A101D, A375, SK-MEL-28, G-361, and BRO); Colorectal cancer cell lines (COLO 205, HT-29, LS411N, and HCT-116) Concentration: 0.9-6000 nM Incubation Time: 3 days Result: Showed a EC50 range of 1-10 nM in an extended panel of BRAF-mutant human melanoma and colorectal cancer cell; while proliferation of BRAF WT cells was inhibited with EC50>1μM. Western Blot Analysis[1] Cell Line: BRAFV600E-mutant A375 cells; BRAF WT, NRAS-mutant BRO (WT BRO) cells Concentration: 0.1-100 nM; 0.1-3000 nM Incubation Time: 2 hours; 24 hours Result: Resulted in a reduction of phospho-MEK1/2 signals. |
| In Vivo | BI-882370 (deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks) is efficacious in multiple mouse models of BRAF-mutant melanomas and colorectal carcinomas, shows superior efficacy compared with Vemurafenib, Dabrafenib, or Trametinib[1]. BI-882370 (deliver orally; 25 mg/kg; twice daily; 40 days) developes resistance within 3 weeks, but resistance is not observed during 5 weeks of second-line therapy in combination with trametinib[1]. BI-882370 (deliver orally; 60 mg/kg; once daily; 2 weeks) indicates lack of toxicity in terms of clinical chemistry, hematology, pathology, and toxicogenomics in rats[1]. Animal Model: Human melanoma xenografts in nude mice with BRAF-mutant melanomas and colorectal carcinomas cells (A375, COLO 205; G-361, HT-29 cells)[1] Dosage: 25 mg/kg; 50 mg/kg Administration: Deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks Result: Regressed tumors partially, upon discontinuation, tumor regrowth was markedly delayed. |
| References | [1]. A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation. Mol Cancer Ther. 2016 Mar;15(3):354-65 |
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