Background:

IC50: 14 μM

Monastrol is a cell-permeable small molecule inhibitor of the mitotic kinesin, Eg5. Like other kinesins, Eg5 can drive the movement of microtubules in vitro.

In vitro: Previous study found that monastrol did not inhibit progression through S and G2 phases of the cell cycle or centrosome duplication. The mitotic arrest due to monastrol was also reversible rapidly. Chromosomes in monastrol-treated cells frequently had both sister kinetochores attached to microtubules extending to the center of the monoaster. Monastrol also inhibited bipolar spindle formation in Xenopus egg extracts, however, monastrol did not prevent the targeting of Eg5 to the monoastral spindles that form [1].

In vivo: Previous study investigated the rat PK and TK of LaSOM 65, a monastrol derivative. Results showed that LaSOM 65 had good bioavailability and linear PK after oral doses. LaSOM 65 distributed consistently in lung and fatty tissues. Other investigated tissues presented smaller penetration ratios. Adverse symptoms were observed only after iv administration, and regressed 3 h after dosing. No statistical differences were found for serum analysis, body weight and relative organ weight, indicating no acute toxicological effects. [2].

Clinical trial: Up to now, LaSOM 65 is still in the preclinical development stage.

参考文献:
[1] Kapoor TM,Mayer TU,Coughlin ML,Mitchison TJ.  Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol.2000 Sep 4;150(5):975-88.
[2] Torres BG,Ucha Fde T,Pigatto MC,Azeredo FJ,Haas SE,Dallegrave E,Canto RF,Eifler-Lima VL,Dalla Costa T.  Pre-clinical pharmacokinetics and acute toxicological evaluation of a monastrol derivative anticancer candidate LaSOM 65 in rats. Xenobiotica.2014 Mar;44(3):254-63.