Pepstatin A (CAS: 26305-03-3)

C₃₄H₆₃N₅O₉

• Tight-binding, reversible, highly selective inhibitor of acid proteases (aspartyl peptidases), like pepsin, gastricsin, cathepsin E and D, renin, chymosin, bacterial aspartic proteinases and HIV proteases.
• Does not inhibit thiol proteases, neutral proteases or serine proteases.
• Widely used as a research tool in studies of protease mechanisms and biological functions.
• Solubilized γ-secretase and retroviral protease inhibitor.
• Shows antibacterial, antifungal and antiparasitic activity.
• Suppresses p53-dependent apoptosis in lymphoid cells as well as TNFα-induced apoptosis in U937 cells.
• Inhibits degradation of autophagic cargo inside autophagolysosomes.

1. Pepstatin, a new pepsin inhibitor produced by Actinomycetes: H. Umezawa, et al.; J. Antibiot. (Tokyo) 23, 259 (1970)
2. Inhibition of cathepsin D-type proteinase of macrophages by pepstatin, a specific pepsin inhibitor, and other substances: M.H. McAdoo, et al.; Infect. Immun. 7, 655 (1973)
3. Mode of inhibition of acid proteases by pepstatin: J. Jr. Marciniszyn, et al.; J. Biol. Chem. 251, 7088 (1976)
4. Non-specific inhibition of pressor agents in vivo by the renin inhibitor pepstatin A: A.A. Oldham, et al.; J. Hypertens. 2, 157 (1984)
5. Inhibition of aspartic proteases by pepstatin and 3-methylstatine derivatives of pepstatin. Evidence for collected-substrate enzyme inhibition: D.H. Rich, et al.; Biochemistry 24, 3165 (1985)
6. Inhibition of HIV replication in cell culture by the specific aspartic protease inhibitor pepstatin A: K. von der Helm, et al.; FEBS Lett. 247, 349 (1989)
7. Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha: L.P. Deiss, et al.; EMBO J. 15, 3861 (1996)
8. Pepstatin A-sensitive aspartic proteases in lysosome are involved in degradation of the invariant chain and antigen-processing in antigen presenting cells of mice infected with Leishmania major: T. Zhang, et al.; BBRC 276, 693 (2000)
9. Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines: G. Tian, et al.; J. Biol. Chem. 277, 31499 (2002)
10. Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation: H. Yoshida, et al.; J. Biochem. 139, 583 (2006)
11. Pepstatin A alters host cell autophagic machinery and leads to a decrease in influenza A virus production: P. Matarrese, et al.; J. Cell Physiol. 226, 3368 (2011)
12. Inhibition of XMRV and HIV-1 proteases by pepstatin A and acetyl-pepstatin: K. Matuz, et al.; FEBS J. 279, 3276 (2012)