856925-74-1Relevant academic research and scientific papers
Discovery of Selective Inhibitors forIn VitroandIn VivoInterrogation of Skeletal Myosin II
Radnai, Laszlo,Surman, Matthew,Hafenbreidel, Madalyn,Young, Erica J.,Stremel, Rebecca F.,Lin, Li,Bdiri, Bilel,Pasetto, Paolo,Jin, Xiaomin,Geedy, Mackenzie,Partridge, Joni-Rae,Patel, Aagam,Conlon, Michael,Sellers, James R.,Cameron, Michael D.,Rumbaugh, Gavin,Griffin, Patrick R.,Kamenecka, Theodore M.,Miller, Courtney A.
, p. 2164 - 2173 (2021/10/12)
Myosin IIs, actin-based motors that utilize the chemical energy of adenosine 5′-triphosphate (ATP) to generate force, have potential as therapeutic targets. Their heavy chains differentiate the family into muscle (skeletal [SkMII], cardiac, smooth) and nonmuscle myosin IIs. Despite the therapeutic potential for muscle disorders, SkMII-specific inhibitors have not been reported and characterized. Here, we present the discovery, synthesis, and characterization of “skeletostatins,” novel derivatives of the pan-myosin II inhibitor blebbistatin, with selectivity 40- to 170-fold for SkMII over all other myosin II family members. In addition, the skeletostatins bear improved potency, solubility, and photostability, without cytotoxicity. Based on its optimalin vitroprofile, MT-134’sin vivotolerability, efficacy, and pharmacokinetics were determined. MT-134 was well-tolerated in mice, impaired motor performance, and had excellent exposure in muscles. Skeletostatins are useful probes for basic research and a strong starting point for drug development.
Absolute stereochemical assignment and fluorescence tuning of the small molecule tool, (-)-blebbistatin
Lucas-Lopez, Cristina,Patterson, Stephen,Blum, Till,Straight, Aaron F.,Toth, Judit,Slawin, Alexandra M. Z.,Mitchison, Timothy J.,Sellers, James R.,Westwood, Nicholas J.
, p. 1736 - 1740 (2007/10/03)
(-)-Blebbistatin (1), a recently discovered small molecule inhibitor of the ATPase activity of non-muscle myosin II has been prepared from methyl 5-methylanthranilate (6) in three steps. This flexible synthetic route has also been used to prepare a nitro
