Uses
PD 145305 is an inactive analog of PD 150606 , a selective inhibitor of calpains (Kis = 0.21 and 0.37 μM for μ- and m-calpain, respectively). It is inactive at concentrations up to 500 μM.
Biological Activity
pd 145305 is an inactive analog of pd 150606, a potent and selective calpains inhibitor [1].calpain is a class of cytosolic cysteine protease that is activated by elevated intracellular calcium. overactivation of calpain has been implicated in the pathophysiology of several degenerative conditions, including stroke, myocardial ischemia, neuromuscular degeneration, and cataract formation [1].pd 145305 is an inactive analog of pd 150606, a potent and selective calpains inhibitor. pd 150606, an alpha-mercaptoacrylate derivative, inhibited μ-calpain and m-calpain with ki values of 0.21 and 0.37 μm, respectively. pd 145305 was inactive at concentrations up to 500 μm. in human leukemic molt-4 cells, pd150606 inhibited a-spectrin proteolysis in a dose-dependent way and virtually eliminated the formation of the 145-kda fragment at 10 μm, whereas pd145305 did not attenuate a-spectrin breakdown product formation. in fetal rat cerebrocortical cultures subjected to a combination of hypoxia and hypoglycemia, pd150606 significantly inhibited the release of lactate dehydrogenase, whereas pd145305 was ineffective. pd150606, but not pd145305, was found to make cerebral glutamatergic neurons more resistant to hypoxic/hypoglycemic challenge [1].
References
[1]. wang kk, nath r, posner a, et al. an alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. proc natl acad sci u s a. 1996 jun 25;93(13):6687-92.
