Z-VAD-FMK
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MedKoo CAT#: 533011

CAS#: 187389-52-2

Description: Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor. Z-VAD-FMK inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM). Z-VAD(OMe)-FMK is an ubiquitin carboxy-terminal hydrolase L1 (UCHL1) inhibitor. Z-VAD(OMe)-FMK irreversibly modifies UCHL1 by targeting the active site of UCHL1.


Chemical Structure

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Z-VAD-FMK
CAS# 187389-52-2

Theoretical Analysis

MedKoo Cat#: 533011
Name: Z-VAD-FMK
CAS#: 187389-52-2
Chemical Formula: C22H30FN3O7
Exact Mass: 467.2068
Molecular Weight: 467.49
Elemental Analysis: C, 56.52; H, 6.47; F, 4.06; N, 8.99; O, 23.96

Price and Availability

Size Price Availability Quantity
2.0mg USD 80.0 Ready to ship
5.0mg USD 150.0 Ready to ship
10.0mg USD 250.0 Ready to ship
25.0mg USD 550.0 Ready to ship
50.0mg USD 850.0 Ready to ship
100.0mg USD 1250.0 Ready to ship
200.0mg USD 1950.0 Ready to ship
500.0mg USD 3650.0 Ready to ship
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Synonym: Z-VAD-FMK; Z VADFMK; ZVADFMK; Z-VAD(OMe)-FMK; Z-Val-Ala-Asp(OMe)-FMK;

IUPAC/Chemical Name: methyl (3S)-5-fluoro-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoate

InChi Key: MIFGOLAMNLSLGH-QOKNQOGYSA-N

InChi Code: InChI=1S/C22H30FN3O7/c1-13(2)19(26-22(31)33-12-15-8-6-5-7-9-15)21(30)24-14(3)20(29)25-16(17(27)11-23)10-18(28)32-4/h5-9,13-14,16,19H,10-12H2,1-4H3,(H,24,30)(H,25,29)(H,26,31)/t14-,16-,19-/m0/s1

SMILES Code: O=C(OC)C[C@H](NC([C@@H](NC([C@@H](NC(OCC1=CC=CC=C1)=O)C(C)C)=O)C)=O)C(CF)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Z-VAD(OMe)-FMK (Z-Val-Ala-Asp(OMe)-FMK) is a cell-permeable and irreversible pan-caspase inhibitor as well as an ubiquitin carboxy-terminal hydrolase L1 (UCHL1) inhibitor that irreversibly modifies UCHL1 by targeting the active site of UCHL1.
In vitro activity: To evaluate the anti-apoptotic effect of the pan-caspase inhibitor Z-VAD-FMK on the three granulosa cell lines, apoptosis was induced by etoposide, a topoisomerase II inhibitor that stabilizes DNA double strand breaks. Z-VAD-FMK treatment inhibited the etoposide-induced decrease in metabolic activity of the granulosa cells. Flow cytometry experiments also indicated a protective effect of Z-VAD-FMK against etoposide by showing a higher number of viable cells when the cells were treated with both drugs compared with treatment with etoposide alone (Fig. 1a–f). . Using Western blotting, the expression levels of the apoptosis-related proteins were studied. In the GC1a cells, p53 expression was decreased by etoposide, whereas the opposite was observed in the COV434 cells. The addition of Z-VAD-FMK decreased p53 expression in the COV434 cells but had no effect in the GC1a cells. Full-length PARP expression levels increased in the GC1a and HGL5 cells after Z-VAD-FMK treatment (Fig. 4g–i). The assessment of metabolic activity and FACS analyses in the normoxic experiments indicate that Z-VAD-FMK protects granulosa cells from etoposide-induced cell death. Reference: J Assist Reprod Genet. 2015 Oct; 32(10): 1551–1559. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615917/
In vivo activity: After establishing that zVAD can reduce the mortality of mice undergoing endotoxin shock, the effects of zVAD on LPS-induced pathology were next assessed. Mice were pretreated with various doses of zVAD for 2 h followed by LPS challenge for 12 h and then pathological lesions were observed. In contrast to mice treated with LPS and zVAD, obvious liver and lung pathology, such as hepatocyte karyolysis, karyopyknosis, inflammatory cell infiltration and disordered hepatic cord arrangement, could be observed in the LPS-challenged group (Figures 3A,B). Furthermore, the MPO activity also indicated that the infiltration of neutrophils in liver and lung were decreased after treated with zVAD (Figure S10). Moreover, TUNEL staining revealed that the percentage of apoptotic cells in lung and liver tissues from LPS and zVAD treated mice was significantly reduced compared to that from LPS-treated mice (Figures 3C,D). Based on these data, it has been demonstrated that zVAD can ameliorate LPS-induced lung and liver injuries and inhibit LPSinduced pro-inflammatory responses Reference: Front Immunol. 2019; 10: 1824. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687755/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 52.0 111.23

Preparing Stock Solutions

The following data is based on the product molecular weight 467.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Fransolet M, Henry L, Labied S, Noël A, Nisolle M, Munaut C. In vitro evaluation of the anti-apoptotic drug Z-VAD-FMK on human ovarian granulosa cell lines for further use in ovarian tissue transplantation. J Assist Reprod Genet. 2015 Oct;32(10):1551-9. doi: 10.1007/s10815-015-0536-9. Epub 2015 Jul 14. PMID: 26169075; PMCID: PMC4615917. 2. Fransolet M, Noël L, Henry L, Labied S, Blacher S, Nisolle M, Munaut C. Evaluation of Z-VAD-FMK as an anti-apoptotic drug to prevent granulosa cell apoptosis and follicular death after human ovarian tissue transplantation. J Assist Reprod Genet. 2019 Feb;36(2):349-359. doi: 10.1007/s10815-018-1353-8. Epub 2018 Nov 3. PMID: 30390176; PMCID: PMC6420548. 3. Li X, Yao X, Zhu Y, Zhang H, Wang H, Ma Q, Yan F, Yang Y, Zhang J, Shi H, Ning Z, Dai J, Li Z, Li C, Su F, Xue Y, Meng X, Dong G, Xiong H. The Caspase Inhibitor Z-VAD-FMK Alleviates Endotoxic Shock via Inducing Macrophages Necroptosis and Promoting MDSCs-Mediated Inhibition of Macrophages Activation. Front Immunol. 2019 Aug 2;10:1824. doi: 10.3389/fimmu.2019.01824. PMID: 31428103; PMCID: PMC6687755. 4. Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E. Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model. Infect Dis Obstet Gynecol. 2009;2009:749432. doi: 10.1155/2009/749432. Epub 2009 Dec 28. PMID: 20069051; PMCID: PMC2801448.’
In vitro protocol: 1. Fransolet M, Henry L, Labied S, Noël A, Nisolle M, Munaut C. In vitro evaluation of the anti-apoptotic drug Z-VAD-FMK on human ovarian granulosa cell lines for further use in ovarian tissue transplantation. J Assist Reprod Genet. 2015 Oct;32(10):1551-9. doi: 10.1007/s10815-015-0536-9. Epub 2015 Jul 14. PMID: 26169075; PMCID: PMC4615917. 2. Fransolet M, Noël L, Henry L, Labied S, Blacher S, Nisolle M, Munaut C. Evaluation of Z-VAD-FMK as an anti-apoptotic drug to prevent granulosa cell apoptosis and follicular death after human ovarian tissue transplantation. J Assist Reprod Genet. 2019 Feb;36(2):349-359. doi: 10.1007/s10815-018-1353-8. Epub 2018 Nov 3. PMID: 30390176; PMCID: PMC6420548.
In vivo protocol: 1. Li X, Yao X, Zhu Y, Zhang H, Wang H, Ma Q, Yan F, Yang Y, Zhang J, Shi H, Ning Z, Dai J, Li Z, Li C, Su F, Xue Y, Meng X, Dong G, Xiong H. The Caspase Inhibitor Z-VAD-FMK Alleviates Endotoxic Shock via Inducing Macrophages Necroptosis and Promoting MDSCs-Mediated Inhibition of Macrophages Activation. Front Immunol. 2019 Aug 2;10:1824. doi: 10.3389/fimmu.2019.01824. PMID: 31428103; PMCID: PMC6687755. 2. Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E. Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model. Infect Dis Obstet Gynecol. 2009;2009:749432. doi: 10.1155/2009/749432. Epub 2009 Dec 28. PMID: 20069051; PMCID: PMC2801448.’

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Bassi C, Fortin J, Snow BE, Wakeham A, Ho J, Haight J, You-Ten A, Cianci E, Buckler L, Gorrini C, Stambolic V, Mak TW. The PTEN and ATM axis controls the G1/S cell cycle checkpoint and tumorigenesis in HER2-positive breast cancer. Cell Death Differ. 2021 May 31. doi: 10.1038/s41418-021-00799-8. Epub ahead of print. PMID: 34059798.

1. Slee EA1, Zhu H, Chow SC et al. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem J. 1996 Apr 1;315 ( Pt 1):21-4.

2. Lawrence CP1, Chow SC. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties. Toxicol Appl Pharmacol. 2012 Nov 15;265(1):103-12.