Biological Activity
arq 621 is a novel, allosteric,potent and selective inhibitor of eg5. eg5 is a member of the mitotickinesin superfamily which plays a key role in mitosis. eg5 is essential for the dynamic organization of the mitotic spindle. over-expression of eg5 leads to genomic instability and tumor formation [1].
in vitro
in human liver microsomes, t1/2 of arq 621 was 53 min. the t1/2value of arq 621 in male and female mouse, rat, dog and monkey liver microsomes was 43, 53, 56, 53, 47, 44, 36, and 32 minutes, respectively [1]. ic50value of arq 621 for cyp 1a2, 2c9, 2d6, 3a4, 2c19, and 2c8 was>20, >20, >20, 4.1, 4.0, and 15 μm, respectively. arq 621 showed anti-tumor activity with potencies in the low nanomolar range across a range of human solid and hematological malignanciescancer cell types such as colon, nsclc, gastric, and hematologic cancer cell lines [1].
in vivo
oral administration of arq 621 showed that the bioavailability of arq 621 was approximately 9% [1].
References
savage r e, zhong c, hall t, et al. in vitro adme properties of arq 621: a specific eg5 inhibitor[j]. cancer research, 2010, 70(8 supplement): 5783-5783.rosen l, chen l c, iyengar t, et al. arq 621, a novel potent and selective inhibitor of eg5: preclinical data and early results from a clinical phase 1 study[j]. cancer research, 2010, 70(8 supplement): 2750-2750.chen l c, rosen l s, iyengar t, et al. first-in-human study with arq 621, a novel inhibitor of eg5: final results from the solid tumors cohort[c]//asco annual meeting proceedings. 2011, 29(15_suppl): 3076.
