UCF-101

Mammalian Omi/HtrA2 is a serine protease localized in mitochondria with close homology to bacterial HtrA chaperones. It is released from the mitochondria in response to apoptotic stimuli whereupon it induces cell death through both a caspase-dependent manner and a mechanism that involves its protease activity. UCF 101 is an inhibitor of the proteolytic activity of Omi/HtrA2 (IC50 = 9.5 μM). It is highly specific for Omi/HtrA2, demonstrating less potent activity when tested against a panel of various other serine proteases (IC50s range from 200 to >500 μM). Additionally, UCF 101 is naturally fluorescent, thus enabling the visualization of its entry into cells. UCF 101 has been used to decrease cerebral infarct size in a rat model of cerebral ischemia, demonstrating neuroprotective effects by reducing apoptosis of cortical cells. It has also been reported to be protective of cardiomyocytes against ischemic injury through a mechanism that prevents Omi/HtrA2 proteolysis of Thanatos-associated protein 5, a cardiac-specific nuclear protein that controls cell cycle progression.