TAK-659 HCl

Description: TAK-659 hydrochloride is a novel, potent, highly selective and orally bioavailable spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM. TAK-659 shows inhibition toward a SYK-dependent cell line (OCILY10) in a cell proliferation assay. TAK-659 is shown to be able to inhibit the growth of FLT3-ITD dependent cell lines, MV4-11 and MOLM-13 while the WT FLT3 RS4-11 (ALL cell line) and RA1 (Burkitt’s Lymphoma cell line) are not sensitive toward TAK-659. The sensitivity to TAK-659 is associated with mutations impacting SYK activity in B cell lymphomas, whereas TAK-659 is not cytotoxic for adherent primary or solid tumor cell lines. TAK-659 inhibits the microenvironment-induced activation of Syk and downstream signaling molecules, without inhibiting the protein homologue ZAP-70 in T cells. Importantly, the pro-survival, proliferative, chemoresistant and activation effects promoted by the microenvironment are abrogated by TAK-659, which furthermore blocks CLL cell migration toward BMSC, CXCL12, and CXCL13.

References: Bioorg Med Chem Lett. 2016 Dec 15; 26(24):5947-5950; Oncotarget. 2017 Jan 3; 8(1):742-756.

Related CAS:1312691-33-0 (free base); 1312691-41-0 (2HCl)