In vitro activity: Pepstatin A is a potent aspartic protease inhibitor, and also inhibits HIV replication. Pepstatin A shows effective inhibition on aspartic proteinases such as pepsin, cathepsins D and E. In HIV-infected H9 cells, pepstatin A inhibits part of the intracellular processing of the HIV gag protein with no apparent toxicity on HIV-infected cells. Pepstatin A laos suppresses the differentiation of osteoclasts by blocking ERK signaling and the inhibition of NFATc1 expression.

Kinase Assay: Pepstatin A is a well-known inhibitor of aspartic proteinases with IC50 values of 15 μM, 2 μM, < 5 nM and < 40 nM for human renin, HIV protease, pepsin and cathepsin D, respectively.

Cell Assay: Pepstatin A is a pentapeptide. It was originally isolated from the microbe. As a most potent renin inhibitor, pepstatinA inhibited porcine renin and human renin at weak acid pH value with IC50 values of 0.32 and 15 μM, respectively. The disadvantage is that, pepstatin Ais hydrophobic. To couple the charged hydrophilic residues to the C-terminal of pepstatinA can increase its solubility. Besides the renin, pepstatin A was also reported to have inhibitory effects on HIV protease and subsequently suppressed the virus replication. In cultured H9 cells, pepstatinA treatment blocked the proteolytic processing of the virus gag precursor and inhibited the production of infectious HIV. Moreover, pepstatin A was found to inhibit osteoclast differentiation due to its inhibitory efficacy of cathepsin D and E.

Proc Natl Acad Sci U S A. 1988 Sep;85(18):6612-6; J Biochem. 2006 Mar;139(3):583-90; Biochem J. 1981 Aug 1;197(2):465-71; FEBS Lett. 1993 Mar 22;319(3):253-6.