BTB-1

BTB-1 is a novel small molecule inhibitor of the mitotic motor protein Kif18A, which was identified by Catarinella et al. during a highthroughput screen against Kif18A ’s MT-stimulated ATPase activity, with an IC50 of 1.7 –1.9 M . It is selective within the kinesin subgroup of Kif4, Eg5, MKLP-1, MKLP-2, MPP1, CENP-E and MCAK, and during in vitro motility assays Kif18A ’s MT gliding ability was blocked by the addition of BTB-1 in a reversible manner. BTB-1 was found to be ATP competitive and MT uncompetitive, only inhibiting the ATPase activity of the MT-bound motor protein. BTB-1 could serve as a valuable tool in disentangling the nature of Kif18A ’s double functionality within mitosis and assessing for potential therapeutic utilities.