MKI-2

MKI-2 is a selective MASTL inhibitor with an IC50 of 37.44 nM. MKI-2 induces mitotic catastrophe through modulation of the MASTL–PP2A axis in breast cancer cells. MKI-2 reduces phospho-ENSA, total and phospho-c-Myc levels. MKI-2 inhibits cancer cell proliferation, migration, and induces DNA damage, and also inhibits germinal vesicle breakdown in mouse oocytes. MKI-2 is utilized in biomedical research focused on cell-cycle regulation, mitotic checkpoint control, and MASTL-dependent signaling networks in cancer-associated biological systems.

MASTL:37.44 nM

Methods：In vitro kinase assay, multiple breast cancer cell lines and mouse oocyte models were adopted. Cells were treated with MKI-2 at gradient concentrations for corresponding durations. Kinase activity, signaling pathway, cell cycle, proliferation, invasion and cell viability were detected to evaluate drug efficacy and target selectivity.
Results：
1.MKI-2 potently inhibited recombinant MASTL kinase with an IC₅₀ of 37.44 nM. After 14-hour treatment, it suppressed intracellular MASTL activity in MCF7 cells with an intracellular IC₅₀ of 142.7 nM.
2.MKI-2 presented favorable target selectivity at 100 nM, barely inhibiting ROCK1, PKACα and p70S6K, and exerting only mild effect on AKT1.
3.Treatment at 250 nM regulated the MASTL-PP2A-c-Myc pathway, elevated PP2A activity and downregulated the expression of phosphorylated ENSA and c-Myc.
4.24-hour treatment with 250 nM MKI-2 induced mitotic catastrophe in MCF7 cells, accompanied by mitotic arrest, apoptosis and aggravated DNA damage.
5.MKI-2 broadly suppressed proliferation of various breast cancer cell lines, with IC₅₀ values ranging from 56.53 nM to 124.6 nM after 72-hour incubation. It also impaired cell colony and 3D spheroid formation, and inhibited tumor cell migration and invasion.
6.Low-concentration MKI-2 reduced the germinal vesicle breakdown rate of mouse oocytes without causing obvious damage to cell viability [1].