VLS-1272 (Compound 22) is an orally active KIF18A inhibitor that binds to the KIF18A-microtubule complex in an ATP-noncompetitive manner (IC50 = 41 nM), blocking its ATPase activity and inhibiting microtubule translocation. This leads to abnormal accumulation of KIF18A at spindle poles, disrupting chromosome alignment and inducing mitotic arrest and apoptosis in CINHigh tumor cells (e.g., ovarian cancer OVCAR-3, breast cancer JIMT-1). VLS-1272 is a promising candidate for anti-tumor research[1][2].
in vivo
VLS-1272 (Compound 22; 10-60 mg/kg; p.o.; twice or once a day for 1 month) inhibits HCC15 and OVCAR3 tumor growth in mice[1].
Animal Model:
SCID Beige mice, HCC15 tumor model[1]
Dosage:
10, 30 and 60 mg/kg
Administration:
PO, twice a day for 1 month
Result:
Inhibited tumor growth by 30±15%, 72±6% and 82±9% at 10, 30 and 60 mg/kg, respectively.
Animal Model:
Balb/C nude mice, OVCAR3 tumor model[1]
Dosage:
10, 30 and 60 mg/kg
Administration:
PO, once a day for 1 month
Result:
Inhibited tumor growth by 24±26%, 72±17% and 82±10% at 10, 30 and 60 mg/kg, respectively.
References
[1] COGAN, et al. SPIRO INDOLINE INHIBITORS OF KIF18A. Patent WO2023028564. [2] Phillips AF, et al. Targeting chromosomally unstable tumors with a selective KIF18A inhibitor. Nat Commun. 2025 Jan 2;16(1):307. DOI:10.1038/s41467-024-55300-z
