Pepstatin is a potent inhibitor of aspartyl proteases. It is a hexa-peptide containing the unusual amino acid statine (Sta, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid), having the sequence Isovaleryl-Val-Val-Sta-Ala-Sta (Iva-Val-Val-Sta-Ala-Sta). It was originally isolated from cultures of various species of Actinomyces due to its ability to inhibit pepsin at picomolar concentrations. Pepstatin A is well known to be an inhibitor of aspartic proteinases such as pepsin, cathepsins D and E. Except for its role as a proteinase inhibitor, however, the pharmacological action of pepstatin A upon cells remain unclear. Pepstatin A suppresses receptor activator of NF-κB ligand (RANKL)–induced osteoclast differentiation. Pepstatin A suppresses the formation of multinuclear osteoclasts dose-dependently. This inhibition of the formation only affected osteoclast cells, i.e., not osteoblast-like cells. Furthermore, pepstatin A also suppresses differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose-dependently. This inhibition seems to be independent of the activities of proteinases such as cathepsin D, because the formation of osteoclasts was not suppressed with the concentration that inhibited the activity of cathepsin D. Cell signaling analysis indicated that the phosphorylation of ERK was inhibited in pepstatin A-treated cells, while the phosphorylation of IκB and Akt showed almost no change. Furthermore, pepstatin A decreased the expression of nuclear factor of activated T cells c1 (NFATc1). These results suggest that pepstatin A suppresses the differentiation of osteoclasts through the blockade of ERK signaling and the inhibition of NFATc1 expression.

CAS：26305-03-3
中文别名：抑肽素;胃蛋白酶抑制剂;
英文别名：pepsininhibitors735a;peptistatin A;PEPSTATIN A SYNTHETIC;Isovalerylpepstatin;procidins735a;PepstainA;PEPSTATIN;pepstatine A;ahpatininc;IVA-VAL-VAL-STA-ALA-STA;
分子式：C34H63N5O9
分子量：685.892
精确质量：685.463
Psa：223.26
Logp：3.4217

MDL号：MFCD00060740
PubChem号：24898620
EINECS号：247-600-0
BRN号：2201362
RTECS号：SC6155000

外观与性状：固体
密度：1.117 g/cm3
沸点：997.6ºC at 760 mmHg
熔点：233°C (dec.)(lit.)
闪点：557.1ºC
折射率：1.504
稳定性：Stable. Incompatible with strong bases, strong acids.
储存条件：2-8ºC
蒸汽压：0mmHg at 25°C

RTECS号：SC6155000
安全说明：S22-S24/25
WGK Germany：2