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Chemical Structure| 26305-03-3 Chemical Structure| 26305-03-3

Structure of Pepstatin A
CAS No.: 26305-03-3

Chemical Structure| 26305-03-3

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Pepstatin (Pepstatin A) is a specific, orally active aspartic protease inhibitor produced by actinomycetes, with IC50 values of 4.5 nM for hemoglobin-pepsin, 6.2 nM for hemoglobin-proctase, 150 nM for casein-pepsin, 290 nM for casein-proctase, 520 nM for casein-acid protease, and 260 nM for hemoglobin-acid protease. Pepstatin also inhibits HIV protease.

Synonyms: Pepstatin; NSC 272671; Pepstatinum

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Product Citations

Product Citations

Yao, Jingyue ; Wang, Jubo ; Xu, Ye ; Guo, Qinglong ; Sun, Yuening ; Liu, Jian , et al.

Abstract: Mitophagy is a type of selective macroautophagy/autophagy that degrades dysfunctional or excessive mitochondria. Regulation of this process is critical for maintaining cellular homeostasis and has been closely implicated in acquired drug resistance. However, the regulatory mechanisms and influences of mitophagy in cancer are still unclear. Here, we reported that inhibition of CDK9 blocked PINK1-PRKN-mediated mitophagy in HCC (hepatocellular carcinoma) by interrupting mitophagy initiation. We demonstrated that CDK9 inhibitors promoted dephosphorylation of SIRT1 and promoted FOXO3 protein degradation, which was regulated by its acetylation, leading to the transcriptional repression of FOXO3-driven BNIP3 and impairing the BNIP3-mediated stability of the PINK1 protein. Lysosomal degradation inhibitors could not rescue mitophagy flux blocked by CDK9 inhibitors. Thus, CDK9 inhibitors inactivated the SIRT1-FOXO3-BNIP3 axis and PINK1-PRKN pathway to subsequently block mitophagy initiation. Moreover, CDK9 inhibitors facilitated mitochondrial dysfunction. The dual effects of CDK9 inhibitors resulted in the destruction of mitochondrial homeostasis and cell death in HCC. Importantly, a novel CDK9 inhibitor, oroxylin A (OA), from Scutellaria baicalensis was investigated, and it showed strong therapeutic potential against HCC and a striking capacity to overcome drug resistance by downregulating PINK1-PRKN-mediated mitophagy. Additionally, because of the moderate and controlled inhibition of CDK9, OA not led to extreme repression of general transcription and appeared to overcome the inconsistent anti-HCC efficacy and high normal tissue toxicity that was associated with existing CDK9 inhibitors. All of the findings reveal that mitophagy disruption is a promising strategy for HCC treatment and OA is a potential candidate for the development of mitophagy inhibitors.

Keywords: CDK9 ; drug resistance ; hepatocellular carcinoma ; mitophagy ; PINK1-PRKN

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Product Details of Pepstatin A

CAS No. :26305-03-3
Formula : C34H63N5O9
M.W : 685.89
SMILES Code : CC(C)CC(N[C@@H](C(C)C)C(N[C@@H](C(C)C)C(N[C@@H](CC(C)C)[C@@H](O)CC(N[C@@H](C)C(N[C@@H](CC(C)C)[C@@H](O)CC(O)=O)=O)=O)=O)=O)=O
Synonyms :
Pepstatin; NSC 272671; Pepstatinum
MDL No. :MFCD00060740
InChI Key :FAXGPCHRFPCXOO-LXTPJMTPSA-N
Pubchem ID :5478883

Safety of Pepstatin A

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.46mL

0.29mL

0.15mL

7.29mL

1.46mL

0.73mL

14.58mL

2.92mL

1.46mL

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