BI-3406

• CAS: 2230836-55-0
• Catalog Number: ACM2230836550
• Category: Inhibitors
• Molecular Weight: 462.47
• Molecular Formula: C23H25F3N4O3
• Description: BI-3406 is Potent & Selective SOS1::KRAS Inhibitor (IC50=5 nM), which Opens a New Approach for Treating KRAS-Driven Tumours. BI 3406 selectively binds to SOS1 and blocks the interaction with KRAS, irrespective of the KRAS mutation. BI 3406 causes RAS GTP and pERK reduction and inhibits cell growth of KRAS mutated cell lines, carrying most of the typical KRAS mutations (i.e. G12D, G12V, G13D and others). BI 3406, when administered orally to tumour bearing mice, causes a dose dependent tumour static effect that can be converted into regressions when combined with MEK1 inhibition.
• Synonyms: BI-3406; BI 3406; BI3406
• IUPAC Name: N-((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)-7-methoxy-2-methyl-6-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-4-amine
• Canonical SMILES: C[C@H](C1=CC(N)=CC(C(F)(F)F)=C1)NC2=C3C(C=C(OC)C(O[C@H]4CCOC4)=C3)=NC(C)=N2
• InChI: InChI=1S/C23H25F3N4O3/c1-12(14-6-15(23(24,25)26)8-16(27)7-14)28-22-18-9-21(33-17-4-5-32-11-17)20(31-3)10-19(18)29-13(2)30-22/h6-10,12,17H,4-5,11,27H2,1-3H3,(H,28,29,30)/t12-,17+/m1/s1
• InChI Key: XVFDNRYZXDHTHT-PXAZEXFGSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: BI-3406 is an inhibitor of the interaction between KRAS and SOS1 with an IC50 of 6 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 59.73; H, 5.45; F, 12.32; N, 12.11; O, 10.38
• Exact Mass: 462.1879
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To investigate whether BI-3406 was capable of cellular SOS1 inhibition, cells were treated with increasing concentrations of BI-3406. The compound inhibited RAS-GTP levels with an IC50 of 83-231 nM in SOS1/KRAS-dependent NCI-H358 (KRAS G12C) and A549 (KRAS G12S) cells (Fig. 1g). Furthermore, BI-3406 inhibited the 3D growth of 4 KRAS mutant cancer cells with a IC50 of 16-52 nM, as half-maximum inhibitory concentration (Fig. 2b). Collectively, these data show a clear correlation between signaling pathway and growth inhibition by BI-3406 in KRAS-driven cancer cell lines.; Reference: Cancer Discov. 2021 Jan;11(1):142-157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892644/
• In Vivo Activity: Based on its potent cellular activity and favorable pharmacokinetic properties, the efficacy of BI-3406 was evaluated in established, subcutaneous KRAS G12C-mutated MIA PaCa-2 xenografts. Twice daily treatment with either 12 or 50 mg/kg of BI-3406 was well tolerated and resulted in a prolonged dose-dependent tumor growth inhibition (p<0.005 as compared to vehicle control, Fig. 3d, 3e). Similar tumor growth inhibitory effects were observed in KRAS G12V-mutated SW620, the KRAS G13D-mutated LoVo and the KRAS G12S-mutated A549 xenograft models (Fig. 3f, Supplementary Fig. S3i and S3j). Thus, oral administration of BI-3406 monotherapy inhibits the growth of KRAS G12C, G12V, G13D and G12S mutated xenograft models.; Reference: Cancer Discov. 2021 Jan;11(1):142-157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892644/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).