ALW-II-41-27

ALW-II-41-27 is a multi-kinase inhibitor that inhibits EphB2, EphA3, Kit, FMS, VEGFR2/KDR, FLT1, FGR, Src, Lyn, BMX, and Bcr-Abl in tyrosine kinase-transformed Ba/F3 cells (EC₅₀s = <500 nM).¹ ALW-II-41-27 also inhibits DDR2 and Src (IC₅₀s = 51 and 14 nM, respectively) as well as wild-type and mutant RET kinases (IC₅₀s = 24.7, 94.2, and 15.8 nM for wild-type, RET^V804L, and RET^V804M, respectively).^2,3 It reduces growth of NCI-H2286 and HCC-366 cancer cells (GI₅₀s = 0.51 and 0.65 μM, respectively) and RAT1 cells transformed by RET^C634R or RET^M918T (IC₅₀s = 44 and 56 nM, respectively). ALW-II-41-27 also inhibits growth of MDA-MB-231 breast cancer cells in a concentration-dependent manner and inhibits tumor growth in vivo in a mouse patient-derived xenograft (PDX) model of EphA2-overexpressing triple-negative breast cancer (TNBC).⁴

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1. Choi, Y., Syeda, F., Walker, J.R., et al. Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett. 19(15), 4467-4470 (2009).

2. Terai, H., Tan, L., Beauchamp, E.M., et al. Characterization of DDR2 inhibitors for the treatment of DDR2 mutated nonsmall cell lung cancer. ACS Chem. Biol. 10(12), 2687-2696 (2015).

3. Moccia, M., Liu, Q., Guida, T., et al. Identification of novel small molecule inhibitors of oncogenic RET kinase. PLoS One 10(6), e0128364 (2015).

4. Song, W., Hwang, Y., Youngblood, V.M., et al. Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers. Oncogene 36(40), 5620-5630 (2017).