Home Cart Sign in  
Chemical Structure| 88321-09-9 Chemical Structure| 88321-09-9

Structure of E-64d
CAS No.: 88321-09-9

Chemical Structure| 88321-09-9

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

Aloxistatin (E64d) is a cell-permeable, irreversible, broad-spectrum cysteine protease inhibitor that exhibits an entry-blocking effect for MERS-CoV.

Synonyms: E64c ethyl ester; Aloxistatin; ethyl ester Loxistatin

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

DE Stock

US Stock

Asia Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
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

Purchased from AmBeed: ; ; ; 88899-55-2

Alternative Products

Product Details of E-64d

CAS No. :88321-09-9
Formula : C17H30N2O5
M.W : 342.43
SMILES Code : O=C([C@H]1O[C@@H]1C(N[C@@H](CC(C)C)C(NCCC(C)C)=O)=O)OCC
Synonyms :
E64c ethyl ester; Aloxistatin; ethyl ester Loxistatin
MDL No. :MFCD00132883
InChI Key :SRVFFFJZQVENJC-IHRRRGAJSA-N
Pubchem ID :65663

Safety of E-64d

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

Related Pathways of E-64d

pyroptosis

Isoform Comparison

Biological Activity

Target
  • Cysteine Protease

In Vitro:

Cell Line
Concentration Treated Time Description References
SH-SY5Y cells 10 µM 2 weeks To study the inhibitory effect of E-64d on autophagy Cell Death Dis. 2012 May 24;3(5):e312.
WT or patient fibroblast cells 10 μM 30 min To evaluate the effect of E-64d on lysosomal function in fibroblasts. Results showed that pretreatment with E-64d significantly reduced the activity of lysosomes labeled with BMV109. JCI Insight. 2022 Jul 8;7(13):e158457.
293T cells 10 μM 2 h In CD9KO cells, E-64d significantly reduced MERS pseudovirus entry, indicating the necessity of CD9 in TTSP-mediated early virus entry. PLoS Pathog. 2017 Jul 31;13(7):e1006546.
Huh-7 cells 6 mM 6 h Used to measure autophagic degradation capability, results showed that lysosomal proteolytic activity was markedly reduced in the absence of VTRNA1-1. Autophagy. 2022 Jan;18(1):191-203.
Hepa1-6 cells 10 µM 15 min To determine the proportion of intracellular sporozoites that had productively invaded the cells, rather than those in the process of migrating. J Exp Med. 2011 Feb 14;208(2):341-56.
Huh7 cells 0.14, 0.42, 1.23, 3.7, 11.1, and 33.3 μM 24 h E-64d significantly inhibited SARS-CoV-2 pseudovirus infection with low cytotoxicity. Signal Transduct Target Ther. 2021 Mar 27;6(1):134.
Arabidopsis protoplasts 20 µM 12 h E-64d inhibited the degradation of FBA8, indicating its role in autophagy-associated vacuolar degradation Plant Cell. 2022 Sep 27;34(10):3936-3960.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Humanized mice Humanized ACE2 mice Intraperitoneal injection 12.5 mg/kg Once daily for 2 days E-64d significantly prevented SARS-CoV-2 pseudovirus infection. Signal Transduct Target Ther. 2021 Mar 27;6(1):134.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.92mL

0.58mL

0.29mL

14.60mL

2.92mL

1.46mL

29.20mL

5.84mL

2.92mL

References

 

Historical Records

Categories