KMG-732

KMG-732 (10 μM; 90 min) potently inhibits the polymerization of purified tubulin in vitro, with a V_max of 13.95 mO.D./min^[1].
KMG-732 (0.78-12.5 μM; 300 sec) exhibits binding affinity for purified tubulin in vitro, with a K_d value of 19.3 μM^[1].
KMG-732 (1000 nM; 1 h) binds selectively and potently to purified GAK kinase in vitro with a K_d of 12.0 nM, while exhibiting extremely weak binding affinity toward most other tested kinases^[1].
KMG-732 potently inhibits the activity of purified GAK kinase in vitro, with an IC₅₀ of 73 nM^[1].
KMG-732 (serial concentrations; 72 h) exhibits broad-spectrum antiproliferative activity against various human cancer cell lines in vitro: the GI50 values against pancreatic cancer Mia-paca2, KP2, and BxPC3 cells are 2.97, 10.84, and 16.46 nM, respectively; the GI50 values against colorectal cancer HCT116 and DLD-1 cells are 20.15 and 16.62 nM, respectively; the GI50 values against lung cancer A549 and H522 cells are 8.54 and 9.37 nM, respectively; the GI50 values against liver cancer SK-HEP-1 and HepG2 cells are 12.67 and 14.18 nM, respectively; the GI50 values against breast cancer MCF7 and MDA-MB-231 cells are 10.43 and 111.17 nM, respectively^[1].
KMG-732 (0.1 μM; 1-16 h) completely disrupts the microtubule network in HCT116 colorectal cancer cells, which is characterized by perinuclear aggregation of tubulin and disappearance of cytoplasmic filamentous structures; it also induces the translocation of α-tubulin to the depolymerized (soluble) fraction, confirming its microtubule-destabilizing activity^[1].
KMG-732 (1 μM; 6 h) reduces the levels of acetylated and detyrosinated α-tubulin (markers of stable microtubules) in HCT116 colorectal cancer cells within 6 hours of treatment^[1].
KMG-732 (0.1-10 μM; 4 h pre-incubation plus 2 h EBI treatment) competes with the colchicine-site probe EBI for binding to β-tubulin in HCT116 colorectal cancer cells^[1].
KMG-732 (10-100 nM) induces changes in the levels of mitotic regulatory proteins in HCT116 colorectal cancer cells (decreased Wee1 expression, increased Aurora A, Aurora B and Cyclin B1 expression), indicating the occurrence of mitotic arrest^[1].
KMG-732 (0.1 μM; 2-8 h) induces time-dependent G₂/M phase arrest in HCT116, Mia-paca2 and BxPC3 cancer cells in vitro^[1].
KMG-732 (10 nM; 24 h) significantly inhibits migration and invasion of HCT116 colorectal cancer cells in vitro, reducing both migratory and invasive capacities by over 40%, and this effect occurs without a decrease in cell viability^[1].
KMG-732 (0.1-1000 nM; 2 weeks) potently inhibits long-term colony formation of HCT116 colorectal cancer cells in vitro, with complete inhibition achieved at concentrations ≥100 nM^[1].
KMG-732 (72 h) maintains potent antiproliferative activity in both parental K562 leukemia cells (GI₅₀ = 20.7 nM) and P-gp-overexpressing K562A leukemia cells (GI₅₀ = 14.8 nM).
KMG-732 (0.002-10 μM) exhibits anti-tumor activity in intestinal tumor organoids derived from Apc^(1638n/+) mice, with an IC50 of 0.021 μM[1].