tcsc1081 MLN0905

MLN0905 is a potent PLK1 inhibitor, with an IC₅₀ of 2 nM.

IC50 & Target: IC50: 2 nM (PLK1)^[1]

In Vitro: MLN0905 (compound 12c) exhibits potent activities with an EC₅₀ of 33 ± 21 nM for Cdc25C. MLN0905 shows inhibitory effects on HT29, HCT116, H460, and A375 cell lines, with LD₅₀s of 22, 56, 89, and 34 nM^[1]. MLN0905 (125 nM) yields strong mitotic arrest and monopolar spindle formation in HT-29 cells, and these effects are associated with PLK1 inhibition. MLN0905 suppresses lymphoma cell lines with IC₅₀ values ranging from 3 to 24 nM^[2].

In Vivo: MLN0905 (50 mg/kg, p.o.) shows a higher sustained PD response as it impressively generates a robust PD response up to 72 h in nude mice bearing HT29 xenograft tumors. MLN0905 (6.25, 12.5, 25, 50 mg/kg, p.o.) exhibits significant antitumor activities in mice bearing HT29 xenograft tumors^[1]. MLN0905 has marked antitumor effects in a subcutaneous OCI LY-19-Luc lymphoma xenograft model, and the treatment are as follows: 3.12 mg/kg daily, 6.25 mg/kg daily, 10 mg/kg QD×3/wk, and 14.5 mg/kg QD×3/wk. MLN0905 (1.6, 3.12, and 6.25 mg/kg, p.o.) also induces a significant antitumor response in mice bearing disseminated (human) OCI LY-19-Luc lymphoma disease. MLN0905 (6, 8, 10, 12.5, and 14.5 mg/kg, p.o.) causes a significant antitumor response in a primary human lymphoma model (PHTX-22L). Furthermore, MLN0905 synergizes with rituximab in a disseminated OCI LY-19-Luc lymphoma model^[2].