|S1452||Ispinesib (SB-715992)||<1 mg/mL||103 mg/mL||103 mg/mL|
|S2182||SB743921 HCl||22 mg/mL||111 mg/mL||111 mg/mL|
|S2731||AZ 3146||<1 mg/mL||28 mg/mL||91 mg/mL|
|S7090||GSK923295||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7355||ARQ 621||<1 mg/mL||100 mg/mL||100 mg/mL|
|S8215||BAY 1217389||<1 mg/mL||100 mg/mL||3 mg/mL|
|S8439||Monastrol||<1 mg/mL||58 mg/mL||58 mg/mL|
|S7488||MPI-0479605||<1 mg/mL||62 mg/mL||2 mg/mL|
Ispinesib (SB-715992) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP) with Ki app of 1.7 nM in a cell-free assay, no inhibition to CENP-E, RabK6, MCAK, MKLP1, KHC or Kif1A. Phase 2.
Representative photographs of fluorescent staining of microtubules and nuclei in MDA-MB-231 cells 24 h post-treatment with 4 nM of ispinesib or vinblastine or their combination. Arrows and arrowheads denote mitotic cells with monoploar and bipolar spindles, respectively. Scale bars, 20 um.
SB743921 is a kinesin spindle protein (KSP) inhibitor with Ki of 0.1 nM, almost no affinity to MKLP1, Kin2, Kif1A, Kif15, KHC, Kif4 and CENP-E. Phase 1/2.
HeLa cells expressing iRFP were seeded onto 96-well plates and incubated with buffer or different concentrations of SB743921.During the next ﬁve days, the plate was scanned with an infrared imaging system (upper panel) to quantify the infrared signals (lower panel).
AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM, contributes to recruitment of CENP-E (kinesin-related motor protein), less potent to FAK, JNK1, JNK2, and Kit.
Following single thymidine arrest (STA) for 24 h (the numbers above the arrows indicate the time in hours), cells were released into nocodazole (Noc) for 12 h and then treated with DMSO or Noc plus MG132 (to prevent mitotic exit). After 2 h, cells were processed for immunoprecipitation (IP). cells were synchronized using AZ3146 or other small molecule inhibitors. Cell lysates were then analyzed for BUBR1. Noc, nocodazole.
GSK923295 is a first-in-class, specific allosteric inhibitor of CENP-E kinesin motor ATPase with Ki of 3.2 nM, and less potent to mutant I182 and T183. Phase 1.
(f) HeLa cells were treated with mitotic kinesin CENP-E inhibitor GSK923295 (50 nM) for 1 h to generate misaligned kinetochores. After fixation, cells were stained for ACA, tubulin, and TIP60. Statistical significance was tested by two-sided t-test and represented by asterisks corresponding to ***, p < 0.001. Scale bars, 5 μm.
ARQ 621 is an allosteric, and selective Eg5 mitotic motor protein inhibitor. Phase 1.
BAY 1217389 is an orally bioavailable, selective inhibitor of the serine/threonine kinase monopolar spindle 1 (Mps1) with IC50 values below 10 nmol/L while showing an excellent selectivity profile.
Monastrol is a cell-permeable small molecule inhibitor of kinesin-5(KIF11) which is essential for maintaining separation of the half-spindles.
MPI-0479605 is an ATP competitive and selective inhibitor of mitotic kinase Mps1 with IC50 of 1.8 nM, >40-fold selectivity over other kinases.