tcsc0867 Filanesib

Filanesib (ARRY-520) is a synthetic kinesin spindle protein (KSP) inhibitor with IC₅₀ of 6 nM.

IC50 & Target: IC50: 6 nM (KSP)^[1]

In Vitro: Filanesib (ARRY-520) retains activity in multidrug-resistant cell lines. The EC₅₀s of Filanesib (ARRY-520) for inhibition of proliferation of HCT-15, NCI/ADR-RES and K562/ADR cells are 3.7, 14 and 4.2 nM respectively. Filanesib (ARRY-520) (10 nM) blocks a majority of cells in mitosis with the monopolar spindle structure typical of KSP inhibition^[1]. Filanesib (ARRY-520) (10 nM) induces mitotic arrest as judged by both increased phosphorylation of histone H3 (pHH3) and accumulation of cyclin B1 in four cells^[2]. Filanesib (ARRY-520) and Paclitaxel exhibit the same cytotoxic effect on Type I and II cells. The GI₅₀ at 48 h for Type II EOC cells is 0.0015 μM for ARRY-520. For Type I EOC cells, the GI₅₀ at 48 h is > 3 μM for ARRY-520^[3]. Filanesib (ARRY-520) (1 nM) induces significant G2M cell cycle block in OCI-AML3 cells at 24 hours^[4].

In Vivo: Filanesib (ARRY-520) (10, 15, 20, 30 mg/kg, i.p.) is active in UISO-BCA-1 xenograft, and also superior to paclitaxel in mice bearing subcutaneous HT-29, HCT-116, MDA-MB-231 and A2780 xenografts. ARRY-520 is superior to docetaxel in the androgen receptor-negative prostate cancer xenograft model PC-3, and is also superior to docetaxel in the DU145 prostate xenograft model^[1]. RPMI 8226 tumor xenografts are particularly sensitive to low doses of ARRY-520 (12.5 mg/kg, i.p.)^[2]. ARRY-520 significantly inhibits tumor growth in HL60 and MV4-11 xenografts of SCID mice at concentrations of 27 mg/kg and 20 mg/kg, respectively^[4].