Biochem/physiol Actions

Ispinesib (SB-715992) is a potent and highly selective kinesin spindle protein (KSP, KIF11, EG5) allosteric inhibtor that specifically inhibits microtubule (MT)-stimulated ATPase activity of KSP (K_i = 1.7 nM; 5 µM MT, 500 µM ATP, 0.75 nM human KSP), but not ubiquitous kinesin heavy chain KHC, neuronal kinesin KIF1A, or mitotic kinesins CENP-E, RabK6, MCAK, MKLP1. Ispinesib exhibits anti-cancer efficacy in cultures (GI₅₀ = 45 nM/BT-474 & 19 nM/MDA-MB-468) and in cancer xenograft models in vivo (8 or 10 mg/kg q4d×3 ip. mice with MCF-7, HCC-1954, KPL4, BT-474 xenografts).