Catalog No.: PC-23792Not For Human Use, Lab Use Only.
VLS-1272 is a potent, ATP non-competitive, orally bioavailable, and highly selective inhibitor of KIF18A ATPase activity with IC50 of 41 nM and 8.8 nM for human and murine KIF18A (0.1 mM ATP), respectively.
VLS-1272 is a potent, ATP non-competitive, orally bioavailable, and highly selective inhibitor of KIF18A ATPase activity with IC50 of 41 nM and 8.8 nM for human and murine KIF18A (0.1 mM ATP), respectively. VLS-1272 is an allosteric inhibitor of KIF18A. VLS-1272 is selective for KIF18A over other kinesins, with no inhibition of KIF11/Eg5, KIF18B, or KIFC1 at 100 µM, and an IC50 of 280 nM against KIF19. VLS-1272 prevents cell proliferation to a greater degree in the CINHigh (KIF2A over-expressing) vs. CINLow (KIF2B over-expressing) MDA-MB-231 cell line pair. VLS-1272 demonstrates that the specificity towards cancer cells with chromosome instability differentiates KIF18A inhibition from other clinically tested anti-mitotic drugs. VLS-1272 also induced Caspase-3 cleavage in the sensitive OVCAR-3 cell line but not in the insensitive CAL51 cell line. VLS-1272 (30-60 mg/kg, BID, PO) exhibited robust dose-dependent inhibition of tumor growth in HCC15 and OVCAR-3 tumor models.
