Uses
(2S)-2-(3-Aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide is a known potent kinesin spindle protein inhibitor
Biological Activity
arry 520 trifluoroacetate is a synthetic and salt form of ksp inhibitor with ic50 value of 6 nm.kinesin spindle protein (ksp) is one member of the mitotic kinesins involved in the early stages of mitosis responsible for centrosome separation.
in vitro
arry-520 had low nanomolar antiproliferative activity in various tumor cell lines and exhibited activity in multidrug-resistant cell lines. ec50s of arry-520 for proliferation inhibition in hct-15, nci/adr-res and k562/adr cells was 3.7, 14 and 4.2 nm, respectively, while paclitaxel ec50s in these cell lines was 35, 565 and 372 nm. moreover, k562/adr was found to be 118-fold resistant to paclitaxel when compared to the parent k562 line, but only 3.5-fold resistant to that of arry-520 [1].
in vivo
arry-520 was found to be active in uiso-bca-1 xenografts, which were completely resistant to paclitaxel. the antitumor efficacy of arry-520 was also found to be superior to paclitaxel in mice bearing ht-29, hct-116, mda-mb-231 and a2780 xenografts. arry-520 was superior to docetaxel in the androgen receptor-negative prostate cancer pc-3 xenograft model, and was also superior to docetaxel in the du145 prostate xenograft model [1].
