Pepstatin is a specific aspartic proteases inhibitor produced by actinomycetes, and inhibits the aspartic proteases cathepsin D, pepsin and renin.

Pepstatin is a specific acid protease inhibitor with IC50s of 4.5 nM, 6.2 nM, 150 nM, 290 nM, 520 nM and 260 nM for hemoglobin-pepsin, hemoglobin-proctase, casein-pepsin, casein-proctase, casein-acid protease, and hemoglobin-acid protease, respectively [1]. Pepstatin inhibits the recombinant HIV protease (IC50: 250 μM). Pepstatin shows no effect on cellular protein synthesis and probably does not exert severe cell toxicity [2].

Pepstatin has very low toxicity, with LD50s of 1090 mg/kg, 875 mg/kg, 820 mg/kg and 450 mg/kg for mice, rats, rabbits, and dogs by i.p. route, and > 2000 mg/kg for all species by the oral route. Pepstatin (0.5-50 mg/kg, p.o.) suppresses stomach ulceration of the pylorus in ligated Shay rats [1]. The bacterial motility in the pepstatin-treated gastric juice was measured at the pH values of 2.0, 3.0, 4.0, 4.5, and 5.0 (n = 5 for each pH). The bacteria remained motile significantly longer than in the in vivo experiments without pepstatin [4].

Pepstatin A is freshly dissolved in DMSO at 7 mM. It is very slowly diluted (1:100) into the medium of HIV-infected H9 suspension cultures so that no pepstatin A precipitated (final concentration, 70 μM pepstatin A and 1% DMSO), and the cultures are incubated without change of culture medium for 48 hr. As a control, uninfected H9 cells are also incubated with pepstatin and in addition HIV infected and uninfected cells are incubated with 1% DMSO but without pepstatin [2].

To investigate the effect of pepsins on bacterial motility, similar experiments were performed, but the pepsin in the stomach was inactivated by rinsing the stomach with pepstatin (100 μl of a 2-mg/ml stock solution). Samples were taken and analyzed for bacterial motility at the test pH values of 2.0, 3.0, 4.0, 4.5, and 5.0 and at the same periods after application of the bacterial suspension as in the experiments with active pepsins [4].

26305-03-3

C34H63N5O9

685.904

Pepstatin A;抑肽素;Pepsin Inhibitor S 735A;Ahpatinin C;Pepstatin

[1]Umezawa H, et al. Pepstatin, a new pepsin inhibitor produced by Actinomycetes. J Antibiot (Tokyo). 1970 May;23(5):259-62. [2]Jiang T Y, Feng X F, Fang Z, et al. PTEN deficiency facilitates the therapeutic vulnerability to proteasome inhibitor bortezomib in gallbladder cancer[J]. Cancer Letters. 2020 [3]Schreiber S, et al. Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo. Infect Immun. 2005 Mar;73(3):1584-9. [4]Kim JH, et al. Effects of pepsin and pepstatin on reflux tonsil hypertrophy in vitro. PLoS One. 2018 Nov 8;13(11):e0207090. [5]Seelmeier S, et al. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6612-6.

[1]Jiang T Y, Feng X F, Fang Z, et al. PTEN deficiency facilitates the therapeutic vulnerability to proteasome inhibitor bortezomib in gallbladder cancer. Cancer Letters. 2021, 501: 187-199.

DMSO:25 mg/mL
Ethanol:1 mg/mL (1.46 mM)
H2O:Insoluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years