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Chemical Compound Review:

Ac-DEVD-CHO (4S)-4-[[(2S)-2-acetamido-3- carboxy...

Synonyms: CHEMBL417149, CHEBI:59385, DNC009146, MF 191, AC1LD91U, ...

Jones, R.A. et al., Shi, L. et al., Mariani, S.M. et al., Ruetten, H. et al., Perrin, C. et al., et al.

Zhang, Center, Wu, Cruikshank, Yuan, Andrews, Kornfeld, Mahieux, Pise-Masison, Gessain, Brady, Olivier, Perret, Misteli, Nicot, Miyashita, Nagao, Krajewski, Salvesen, Reed, Inoue, Yamada, Perrin, Ecarnot-Laubriet, Vergely, Rochette, Utaisincharoen, Ubol, Tangthawornchaikul, Chaisuriya, Sirisinha, Krzyzowska, Schollenberger, Skierski, Niemialtowski, Rosenthal, Velena, Chou, Schlegel, Ray, Benton, Anderson, Smith, Simbulan-Rosenthal, Buendia, Santa-Maria, Courvalin,

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Disease relevance of Ac-DEVD-CHO

Melanoma cell apoptosis induced by iNOS inhibition was completely blocked by peptide inhibitors of caspase-1 and caspase-3 (Ac-DEVD-CHO and AC-YVAD-CHO) or by an exogenous NO donor, sodium nitroprusside, or by addition of serum [1].
Ac-DEVD-CHO blocked ischemia/reperfusion-induced caspase-3 activation, but cardiomyocyte apoptosis was unaffected [2].
OBJECTIVES: The aim of this study was to investigate whether the caspase-3 inhibitor Ac-DEVD-CHO functionally improves stunned myocardium [2].
Death was suppressed by Ac-DEVD-CHO and pertussis toxin [3].
Moreover, peptide inhibitor for caspase II subfamily, Ac-DEVD-CHO, reduced the cytolysis of TNF-alpha-treated cholangiocarcinoma cells [4].

High impact information on Ac-DEVD-CHO

Like PARP, cleavage of these substrates in apoptotic cell extracts is abolished by nanomolar concentrations of Ac-DEVD-CHO and micromolar amounts of Ac-YVAD-CHO, confirming the involvement of apopain or an apopain-like activity [5].
In addition, cells undergoing TRAIL-mediated apoptosis displayed cleavage of poly(ADP)-ribose polymerase (PARP) that was completely blocked by Ac-DEVD-CHO [6].
CPP32-like protease activity plays an essential role in this system, as the caspase inhibitor, Ac-DEVD-CHO, strongly inhibited fodrin and lamin B1 cleavage, as well as nuclear morphology changes [7].
This cleavage was inhibited by Ac-DEVD-CHO in a similar manner as that of poly(ADP)ribose polymerase, a known substrate of CPP32/caspase-3 [8].
We conclude that granzyme B activates an ICE-dependent cell death pathway in some cell types and requires a CPP32-like Ac-DEVD-CHO inhibitable protease acting upstream to initiate apoptosis [9].

Chemical compound and disease context of Ac-DEVD-CHO

We investigated the effect of leupeptin and calpain inhibitor-1 (CAI-1), two calpain inhibitors and of a caspase-3 inhibitor, Ac-DEVD-CHO, on functional recovery, myocardial infarct size and apoptosis in isolated rat hearts (Langendorff technique) subjected to 30 min of global ischemia and 120 min of reperfusion [10].

Biological context of Ac-DEVD-CHO

Induction of s-Myc- and c-Myc-mediated apoptotic cell death was effectively prevented by caspase inhibitors such as Z-Asp-CH2-DCB and Ac-DEVD-CHO [11].
A specific caspase-3 inhibitor (Ac-DEVD-CHO) could reverse this phenotype [12].
The activation of CED-3-related caspases was further confirmed by an increase in the rate of Z-DEVD-7-amino-4-trifluoromethylcoumarin (Z-DEVD-AFC) hydrolysis that was sensitive to Ac-DEVD-CHO and was inhibited by pretreatment of the cells with TPCK but not by DCI [13].
Apoptosis, as demonstrated by oligonucleosomal DNA fragmentation and fluorescence microscopy, was induced 24 h after VVC treatment, which was also prevented by caspase-3 inhibitor, Ac-DEVD-CHO [14].
An inhibition of caspase enzyme activity by Ac-DEVD-CHO, a caspase-3 inhibitor, significantly increased cell viability in H(2)O(2)-treated cells [15].

Anatomical context of Ac-DEVD-CHO

Using the peptide inhibitor Ac-DEVD-CHO, apoptosis as well as p45 ICE hydrolysis are suppressed in HeLa cells, suggesting that a CPP32-like protease is upstream of ICE [9].
In addition, we provide the evidence that DNA fragmentation is markedly inhibited by Ac-DEVD-CHO, while cell death, assessed by the damage of the plasma membrane, is marginally inhibited or merely delayed [16].
In this study we demonstrate that endogenous Mst3 is specifically cleaved when Jurkat cells were treated with anti-Fas antibody or staurosporine and that this cleavage is inhibited by the caspase inhibitor, Ac-DEVD-CHO [17].
Pretreatment of keratinocytes with a peptide inhibitor of caspase-3 (Ac-DEVD-CHO) suppressed SM-induced downstream markers of apoptosis [18].
Relevance to pro-IL-16 processing in primary lymphocytes was supported by identifying the p20 subunit of activated caspase-3 in stimulated CD8(+) lymphocytes and by inhibition of CD8(+) lymphocyte lysate-mediated cleavage with Ac-DEVD-CHO [19].

Associations of Ac-DEVD-CHO with other chemical compounds

Pretreatment of the cells with the caspase inhibitors, N-acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO), benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD-FMK), or Z-Asp-2,6-dichlorobenzoyloxymethylketone inhibited anti-Fas-mediated apoptosis [13].
In addition, a caspase-3 inhibitor (Ac-DEVD-CHO) reduced the level of apoptosis, suggesting that DHT/TPA-mediated apoptosis occurs through a caspase-3-dependent pathway [20].
3,4-Dichloroisocoumarin, a serine-protease inhibitor that efficiently inhibits granzyme B and poorly inhibits granzyme A, had similar effects as Ac-DEVD-CHO on anti-CD3 mAb-redirected lysis of L1210 cells [21].
The apopain/Yama inhibitor, Ac-DEVD-CHO, and the proteasome inhibitor, MG-132, were also inactive both in the cell-free system and in whole cells [22].
We also found that the addition of a specific tetrapeptide inhibitor of CPP32/Yama, Ac-DEVD-CHO, provided an effective protection against ceramide-induced cell death [23].

Gene context of Ac-DEVD-CHO

The apoptotic effects of fas agonists in IFN-gamma-treated human and murine FA-C cells were blocked when pretreated with inhibitors (ac-DEVD-cho, CP-DEVD-cho, Z-DEVD-FMK) of the caspase 3 protease [24].
However, DNA fragmentation induced by either allospecific FasL-defective CTL, or by perforin-deficient, TNP-modified, H-2b target cell-specific CTL was prevented in ICE -/- target cells loaded by electroporation with Ac-DEVD-CHO, an inhibitor of CPP32 and related ICE family proteases [25].
While lamin B is cleaved by caspase 6, the protease responsible for the cleavage of LAP2 and Nup153 was probably caspase 3, since (1) cleavage of both proteins was specifically prevented by in vivo addition of caspase 3 inhibitor Ac-DEVD-CHO and (2) consensus sites for these caspases are present in both proteins [26].
When A549 cells were pretreated with the caspase-inhibitory peptide N-acetyl-asp-Glu-Val-Asp-CHO (aldehyde) (Ac-DEVD-CHO), Adv/p16-mediated apoptosis and Rb cleavage were greatly inhibited [27].
In contrast, caspase 3-like activity was observed within minutes of E. histolytica contact and the caspase 3 inhibitor Ac-DEVD-CHO blocked Jurkat T cell death, as measured by both DNA fragmentation and 51Cr release [28].

Analytical, diagnostic and therapeutic context of Ac-DEVD-CHO

Ac-DEVD-CHO was similarly effective when given before reperfusion [2].
When the PN graft was implanted 2 weeks after injury, however, MNs failed to regenerate following Ac-DEVD-CHO treatment, whereas 53% of MNs regenerated their axons into the graft after treatment with Boc-D-FMK [29].
Western blotting and activity measurements showed that caspase-3 was indeed activated, but its peptide inhibitor (Ac-DEVD-CHO) neither suppressed nuclear fragmentation nor rescued the neurons from cell death. z-VAD-fmk, the general inhibitor of caspases, prevented nuclear fragmentation and delayed the cell death [30].
In MNU-treated rats, the TUNEL index 24 hr post-MNU was 79.5% in the peripheral and 83.7% in the central retina, while the Ac-DEVD-CHO injection significantly reduced it to 59.7 and 71.8%, respectively [31].
By using specific caspase inhibitors (Ac-DEVD-CHO, Ac-IETD-CHO and zVAD-fmk), we showed that caspase-3 and -7 (DEVDases) are major effector caspases during EV-induced apoptosis in permissive L929 and RK-13 cell cultures [32].

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