BI-3406
- Optical Purity: 99% d.e.
- Soluble in DMSO
- MF: C23H25F3N4O3
- MW: 462.46
Description
BI-3406 is an orally bioavailable, highly potent and selective KRAS/Son of Sevenless 1 (SOS1) interaction inhibitor (IC50 = 6 nM), binding to the catalytic domain of the guanine nucleotide exchange factor (GEF) SOS1 thereby preventing the interaction with KRAS-GDP. BI-3406 does not block the interaction of KRAS with SOS2 but elicits activity on a broad panel of KRAS oncogenic variants, including all major G12 and G13 oncoproteins. In KRAS-dependent cancers, BI-3406 potently reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling both in vitro and in vivo. Down-modulation of this signaling cascade by BI-3406 in KRAS G12 or G13 mutant cells effectively limits cell proliferation. As a monotherapy, BI-3406 modulates signaling, as assessed by p-ERK and target genes, and displays marked anti-tumor efficacy in KRAS mutant xenografts.
More Information
| Parent CAS No. | 2230836-55-0 |
|---|---|
| Chemical Name | N-((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)-7-methoxy-2-methyl-6-((S)-tetrahydrofuran-3-yloxy)quinazolin-4-amine |
| extra_info | Sold in collaboration with Chemietek |
| SMILES | N1C(N[C@@H](C2C=C(N)C=C(C(F)(F)F)C=2)C)=C2C=C(O[C@H]3CCOC3)C(OC)=CC2=NC=1C |&1:3,20,r| |
| MFCD | N.A. |
| 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 |
| InChiKey | XVFDNRYZXDHTHT-PXAZEXFGSA-N |
| CID | 138911318 |
| Short Description | KRAS-SOS1 inhibitor |
References
- MH Hofmann, et al. Discovery of BI-3406: A potent and selective SOS1::KRAS inhibitor opens a new approach for treating KRAS-driven tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr PL06-01.
- MH Hofmann, et al. BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Cancer Discov. 2021, 11, 142-157.
