OTS-167

OTS-167 (OTSSP-167) is a highly potent and selective MELK inhibitor with IC50 of 0.41 nM; shows anti-proliferative activity for A549, T47D, DU4475, and 22Rv1 cancer cells with IC50 of 6.7, 4.3, 2.3, and 6.0 nM, respectively; inhibits the phosphorylation of PSMA1 and DBNL, two novel MELK substrates and are important for stem-cell characteristics and invasiveness; shows robust tumor growth inhibition (TGI) in xenograft models; orally active.Blood Cancer Phase 2 Clinical (In Vitro) :OTSSP167 inhibits the growth of A549 (lung), T47D (breast), DU4475 (breast), 22Rv1 (prostate) and HT1197 (bladder) cancer cells with IC50 values of 6.7, 4.3, 2.3, 6.0 and 97 nM, respectively. OTSSP167 can abrogate the mitotic checkpoint, disrupt MCC and MCC-APC/C interaction in MCF7 cells. OTSSP167 causes GFP-MELK localization to cell cortex in prometaphase cells. OTSSP167 is a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC50 of 0.41 nM. (In Vivo) :OTSSP167 (20 mg/kg, i.v.) results in tumor growth inhibition (TGI) of 73% in xenograft mouse model; OTSSP167 (1, 5, and 10 mg/kg, p.o.) reveals TGI of 51, 91, and 108%, respectively. OTSSP167 (20 mg/kg, p.o.) shows no tumor growth suppressive effect on PC-14 xenografts.