| Identification | Back Directory | [Name]
BI 882370 | [CAS]
1392429-79-6 | [Synonyms]
CS-2615
BI 882370
BI882370;BI-882370
1-Propanesulfonamide, N-[3-[5-[(1-ethyl-4-piperidinyl)methylamino]-3-(5-pyrimidinyl)-1H-pyrrolo[3,2-b]pyridin-1-yl]-2,4-difluorophenyl]- | [Molecular Formula]
C28H33F2N7O2S | [MDL Number]
MFCD31618072 | [MOL File]
1392429-79-6.mol | [Molecular Weight]
569.67 |
| Chemical Properties | Back Directory | [Boiling point ]
649.6±65.0 °C(Predicted) | [density ]
1.37±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:5.0(Max Conc. mg/mL);8.78(Max Conc. mM) | [form ]
A crystalline solid | [pka]
5.48±0.10(Predicted) | [color ]
Off-white to gray |
| Hazard Information | Back Directory | [Description]
BI-882370 is an orally bioavailable RAF inhibitor with IC50 values of 0.8, 0.8, and 0.6 nM for B-RAFV600E, wild-type B-RAF, and C-RAF in the DFG-out inactive conformation, respectively. It is selective for RAF over a panel of kinases, including LCK, KIT, Src, LYNA, LYNB, and PDGFR (IC50s = 49, 415, 485, 750, 715, and 1,220 nM, respectively). It inhibits proliferation of human B-RAF-mutant melanoma cells when used at concentrations ranging from 1 to 10 nM. It reduces tumor growth in multiple B-RAF-mutant melanoma and colorectal carcinoma mouse xenograft models when administered at a dose of 25 mg/kg twice per day. BI-882370, alone and in combination with trametinib , induces tumor regression in an A375 melanoma mouse xenograft model with no resistance developing within three or five weeks, respectively. | [Uses]
BI-882370 is a potent and selective RAF kinase inhibitor that binds to the ATP binding site of the kinase positioned in the DFG-out (inactive) conformation of the BRAF kinase. BI-882370 (BI 882370) inhibits the oncogenic BRAFV600E-mutant, the WT BRAF and CRAF kinases with IC50s of 0.4, 0.8, and 0.6 nM, respectively. BI-882370 also inhibits SRC family kinases[1]. | [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. |
| [IC 50]
Braf: 0.6 nM (IC50); c-Raf: 0.8 nM (IC50); BRafV600E: 0.4 nM (IC50) | [References]
[1] Waizenegger IC, et al. 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. DOI:10.1158/1535-7163.MCT-15-0617 |
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| Company Name: |
Twochem Co.Ltd.
|
| Telephone: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
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