A1901-1mg | Q-VD-OPh [1135695-98-5] Quimigen Portugal

Background

The broad spectrum caspase inhibitor, QVD-OPh, provides a cost effective, non toxic, and highly speciﬁc means of apoptotic inhibition and provides new insight into the design of new inhibitors¹.

Actinomycin D rapidly induced apoptosis and this was dramatically inhibited by the caspase inhibitor, Q-VD-OPh (quinolyl-valyl-O-methylaspartyl-[-2, 6-diﬂuorophenoxy]-methyl ketone). Q-VD-OPh was signiﬁcantly more effective in preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk. Q-VD-OPh was also equally effective in preventing apoptosis mediated by the three major apoptotic pathways, caspase 9/3, caspase 8/10, and caspase 12. In addition to the increased effectiveness, Q-VD-OPh was not toxic to cells, even at high concentrations.

Q-VD-OPh was equally effective at inhibiting the three major apoptotic pathways, was functional in different cell types and species (human, mouse, and rat) and prevented terminal caspase activation, substrate cleavage, and DNA ladder formation associated with apoptosis. Q-VD-OPh can inhibit recombinant caspases 1, 3, 8, and 9 with IC50 values ranging from 25 to 400 nM². The effectiveness of Q-VD-OPh as an apoptotic inhibitor is evidenced by the complete suppression of an apoptotic inducer capable of inducing substantial cell death in less than 4 hours.

Q-VD-OPh protected against the substantial apoptosis induced by actinomycin D. In addition, Q-VD-OPh alone exhibited little or no toxicity, even at extremely high concentrations.

The effective concentration of Q-VD-OPh may provide a unique reagent when trying to revive hard to propagate cell lines from liquid nitrogen. The addition of this inhibitor to thawed cells would give the cells adequate time to recover, even in the presence of standard DMSO concentrations (10%), from the stress of thawing and begin to proliferate in the absence of toxicity. Q-VD-OPh is stable in solution for several months and is effective in culture for at least 2.5 days. This would provide an ideal time frame for cell recovery; whereas, the subsequent decrease in effectiveness over time would be fortuitous in that the cells would return to standard culture conditions with minimal manipulation¹.

References:
1. T. M. Caserta, A. N. Smith, A. D. Gultice, M. A. Reedy and T. L. Brown, Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties, Apoptosis 2003; 8: 345–352
2. Yin XM. Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res 2000; 10: 161–167

Product Citation

1. Sarah V Schweighofer, Daniel C Jans, et al. "Endogenous BAX and BAK form mosaic rings of variable size and composition on apoptotic mitochondria." Cell Death Differ. 2024 Apr;31(4):469-478. PMID: 38503846
2. Emilie Hollville, et al. "Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry." Curr Protoc. 2023 Dec;3(12):e951. PMID: 38112058
3. Aran Merati, Spandana Kotian, et al. "Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases." Int J Mol Sci. 2023 Sep 5;24(18):13688. PMID: 37761989
4. Anukriti Mathur, Callum Kay, et al. "Clostridium perfringensvirulence factors are nonredundant activators of the NLRP3 inflammasome." EMBO Rep. 2023 Jun 5;24(6):e54600. PMID: 37073791
5. John S H Danial, Andreas Jenner, et al. "Real-Time Growth Kinetics Analysis of Macromolecular Assemblies in Cells with Single Molecule Resolution." J Phys Chem A. 2023 Apr 20;127(15):3490-3496. PMID: 37023388
6. François Le Guerroué, Eric N Bunker, et al. "TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1." Mol Cell. 2023 Mar 16;83(6):927-941.e8. PMID: 36898370
7. Elias Adriaenssens, Thanh Ngoc Nguyen, et al. "Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD." bioRxiv. September 25, 2023.
8. Giridhar Sekar, Geetika Singh, et al. "Small molecule SJ572946 activates BAK to initiate apoptosis." iScience. 2022 Sep 6;25(10):105064. PMID: 36147946
9. Emmanouil Zacharioudakis, Bogos Agianian, et al. "Modulating mitofusins to control mitochondrial function and signaling." Nat Commun. 2022 Jul 7;13(1):3775. PMID: 35798717
10. Hayden Weng Siong Tan, Guang Lu, et al. "A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery." Nat Commun. 2022 Jun 28;13(1):3720. PMID: 35764633
11. Tim Fieblinger, Chang Li, et al. "Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum." Int J Mol Sci. 2022 May 13;23(10):5470. PMID: 35628278
12. Arwen Conod, Marianna Silvano, et al. "On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm." Cell Rep. 2022 Mar 8;38(10):110490. PMID: 35263600
13. Cliff J. Luke, Stephanie Markovina, et al. "Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins." Commun Biol. 2022 Jan 12;5(1):47. PMID: 35022507
14. Shunfei Yan, Jiachen Xuan, et al. "The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer." Br J Cancer. 2021 Feb;124(3):616-627. PMID: 33173151
15. Shahbandi A, Rao SG, et al. "BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer." Cell Death Differ. 2020;10.1038/s41418-020-0564-6. PMID: 32457483
16. Xu Y, Du S, et al. "TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading." Mol Psychiatry. 2020;10.1038/s41380-020-0738-0. PMID: 32366951
17. Sullivan GP, O'Connor H, et al. "TRAIL Receptors Serve as Stress-Associated Molecular Patterns to Promote ER-Stress-Induced Inflammation.". Dev Cell. 2020;S1534-5807(20)30063-0. PMID: 32109381
18. Wang C. "A Sensitive and Quantitative mKeima Assay for Mitophagy via FACS." Curr Protoc Cell Biol. 2020;86(1):e99. PMID: 31876372
19. Shunfei Yan, Piyush B. Madhamshettiwar, et al. "Targeting RNA Polymerase I transcription synergises with TOP1 inhibition in potentiating the DNA damage response in high-grade serous ovarian cancer." bioRxiv. 2019 November 20.
20. Xiaoshan Shi, Adam L. Yokom, et al. "ULK complex organizationin autophagy by a C-shaped FIP200 N-terminal domain dimer." BioRxiv. 2019 Nov. 12.
21. Bahjat M, de Wilde G, et al. "The NEDD8-activating enzyme inhibitor MLN4924 induces DNA damage in Ph+ leukemia and sensitizes for ABL kinase inhibitors." Cell Cycle. 2019 Jul 26:1-16. PMID: 31349760
22. Britt EL, Raman S, et al. "Combination of fenretinide and ABT-263 induces apoptosis through NOXA for head and neck squamous cell carcinoma treatment." PLoS One. 2019 Jul 5;14(7):e0219398. PMID: 31276572
23. Brokatzky D, Dörflinger B, et al. "A non-death function of the mitochondrial apoptosis apparatus in immunity." EMBO J. 2019 Jun 3;38(11). pii:e100907. PMID: 30979778
24. Suresh K, Carino K, et al. "A nonapoptotic endothelial barrier-protective role for caspase-3." Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1118-L1126. PMID: 30908935
25. Vargas JNS, Wang C, et al."Spatiotemporal Control of ULK1 Activation by NDP52 and TBK1 during Selective Autophagy." Mol Cell. 2019 Apr 18;74(2):347-362.e6. PMID: 30853401
26. Allocca M, Corrigan JJ, et al. "Inflammation,necrosis, and the kinase RIP3 are key mediators of AAG-dependentalkylation-induced retinal degeneration." Sci Signal. 2019 Feb 12;12(568). pii:eaau9216. PMID: 30755477
27. Serrano-Saenz S, Palacios C, et al. "PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism." Cell Death Dis. 2019 Jan 18;10(2):51. PMID: 30718520
28. Crifo B, Schaible B, et al. "Hydroxylase Inhibition Selectively Induces Cell Death in Monocytes." J Immunol. 2019 Mar 1;202(5):1521-1530. PMID: 30700584
29. Padman BS, Nguyen TN, et al. "LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy." Nat Commun. 2019 Jan 24;10(1):408. PMID: 30679426
30. Liccardi G, Ramos Garcia L, et al. "RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation." Mol Cell. 2018 Dec 28. pii: S1097-2765(18)30980-8. PMID: 30598363
31. Gehlhausen JR, Hawley E, et al. "A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas." Hum Mol Genet. 2018 Oct 17. PMID: 30335132
32. Ungerleider NA, Rao SG, et al. "Breast cancer survival predicted by TP53 mutation status differs markedly depending on treatment." Breast Cancer Res. 2018 Oct 1;20(1):115. PMID: 30285883
33. Saleh D, Degterev A. "Chemical Library Screens to Identify Pharmacological Modulators of Necroptosis." Methods Mol Biol. 2018;1857:19-33. PMID: 30136227
34. Wang L, Mehta S, et al. "Differential Mechanisms of Septic Human Pulmonary Microvascular Endothelial Cell Barrier Dysfunction Depending on the Presence of Neutrophils." Front Immunol. 2018 Aug 2;9:1743. PMID: 30116240
35. Riley JS, Quarato G, et al. "Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis." EMBO J.2018 Sep 3;37(17). pii: e99238. PMID: 30049712
36. Nicholas R. Ader, Patrick C. Hoffmann, et al. "Molecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis ." bioRxiv. 2018.Aug.1.
37. Liu X, Wang Y, et al. "Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation." Bioorg Med Chem. 2018 Jun 17. pii: S0968-0896(18)30794-6. PMID: 29925484
38. Lu H, Chelvanambi S, et al. "EMAPII Monoclonal Antibody Ameliorates Influenza A Virus-Induced Lung Injury." Mol Ther. 2018 Jun 14. pii: S1525-0016(18)30220-X. PMID: 29910176
39. Dudek AH, Pfaff F, et al. "Partial inactivation of the chromatin remodelers SMARCA2 and SMARCA4 in virus-infected cells by caspase-mediated cleavage." J Virol. 2018 May 30. pii: JVI.00343-18. PMID: 29848589
40. Zheng JH, Grace CR, et al. "Intrinsic Instability of BOK Enables Membrane Permeabilization in Apoptosis." Cell Rep. 2018 May 15;23(7):2083-2094.e6. PMID: 29768206
41. Tammaro A, Florquin S, et al. "S100A8/A9 promotes parenchymal damage and renal fibrosis in obstructive nephropathy." Clin Exp Immunol. 2018 May 10. PMID: 29746703
42. Didier R, Mallavialle A, et al. "Targeting the proteasome-associated deubiquitinating enzyme USP14 impairs melanoma cell survival and overcomes resistance to MAPK-targeting therapies." Mol Cancer Ther.2018 Apr 27. pii: molcanther.0919.2017. PMID: 29703842
43. Joel Riley, Giovanni Quarato, et al. "Activated BAX/BAK enable mitochondrial inner membrane permeabilisation and mtDNA release during cell death."bioRxiv. 2018 February 26.
44. Freedman JC, Navarro MA, et al. "Evidence that Clostridium perfringens Enterotoxin-Induced Intestinal Damage and Enterotoxemic Death in Mice Can Occur Independently of Intestinal Caspase-3 Activation." Infect Immun. 2018 Apr 23. pii: IAI.00931-17. PMID: 29685988
45. Allaway RJ, Wood MD, et al. "Exploiting mitochondrial and metabolic homeostasis as a vulnerability in NF1 deficient cells." Oncotarget. 2017 Jul 18;9(22):15860-15875. PMID: 29662612
46. Charendoff CI, Bouchier-Hayes L. "Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation." J Vis Exp. 2018 Mar 5;(133). PMID: 29553529
47. Lin C, Gu J, et al. "Caspase-dependent apoptosis induction via viral protein ORF4 of porcine circovirus 2 binding to mitochondrial adenine nucleotide translocase 3." J Virol. 2018 Feb 28. pii: JVI.00238-18. PMID: 29491154
48. Danziger O, Pupko T, et al. "Interleukin-6 and Interferon-αSignaling via JAK1-STAT Differentially Regulate Oncolytic versus Cytoprotective Antiviral States." Front Immunol. 2018 Jan 30;9:94. PMID: 29441069
49. Cano-González A, Mauro-Lizcano M, et al."Involvement of both caspase-8 and Noxa-activated pathways in endoplasmic reticulum stress-induced apoptosis in triple-negative breast tumor cells." Cell Death Dis. 2018 Jan 26;9(2):134. PMID: 29374147
50. Campbell KJ, Dhayade S, et al. "MCL-1 is a prognostic indicator and drug target in breast cancer." Cell Death Dis. 2018 Jan 16;9(2):19. PMID: 29339815
51. Anding AL, Wang C, et al. "Vps13D Encodes a Ubiquitin-Binding Protein that Is Required for the Regulation of Mitochondrial Size and Clearance." Curr Biol. 2018 Jan 22;28(2):287-295.e6. PMID: 29307555
52. Le Guerroué F, Eck F, et al. "Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway." Mol Cell. 2017 Nov 16;68(4):786-796.e6. PMID: 29149599
53. Oltean A, Taber LA. "Apoptosis Generates Mechanical Forces that Close the Lens Vesicle in the Chick Embryo." Phys Biol. 2017 Sep 15. PMID: 28914615
54. Yochum ZA, Cades J, et al. "A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer." Mol Cancer Res. 2017 Dec;15(12):1764-1776. PMID: 28851812
55. Giampazolias E, Zunino B, et al. "Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency." Nat Cell Biol. 2017 Sep;19(9):1116-1129. PMID: 28846096
56. Sandlin RD, Wong KHK, et al. "Preservative solution that stabilizes erythrocyte morphology and leukocyte viability under ambient conditions." Sci Rep.2017 Jul 18;7(1):5658. PMID: 28720788
57. Yosef R, Pilpel N, et al. "p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling." EMBO J. 2017 Jun 12. pii: e201695553. PMID: 28607003
58. Murphy T, Melville H, et al. "Knockdown of epigenetic transcriptional co-regulator Brd2a disrupts apoptosis and proper formation of hindbrain and midbrain-hindbrain boundary (MHB) region in zebrafish." Mech Dev. 2017 May 23.pii: S0925-4773(16)30065-X. PMID: 28549975
59. Moraya AI, Ali JL, et al. "Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian cancer cells." J Exp Clin Cancer Res. 2017 May 12;36(1):67. PMID: 28499442
60. Ortega-Atienza S, Krawic C, et al. "20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death." Sci Rep. 2017 Apr 5;7(1):654. PMID: 28381880
61. Iurlaro R, Püschel F, et al. "Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors." Mol Cell Biol. 2017 May 2;37(10). pii: e00479-16. PMID: 28242652
62. Henry CM, Martin SJ. "Caspase-8 Acts in a Non-enzymatic Role as a Scaffold for Assembly of a Pro-inflammatory "FADDosome" Complex upon TRAIL Stimulation. "Mol Cell. 2017 Feb 16;65(4):715-729.e5. PMID: 28212752
63. van Attekum MH, Terpstra S, et al. "Macrophages confer survival signals via CCR1-dependent translational MCL-1 induction in chronic lymphocytic leukemia." Oncogene. 2017 Feb 13. PMID: 28192408
64. Bailey LJ, Alahari S, et al. "Augmented trophoblast cell death in preeclampsia can proceed via ceramide-mediated necroptosis." Cell Death Dis. 2017 Feb 2;8(2):e2590. PMID: 28151467
65. Thorburn J, Staskiewicz L, et al. "Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells." Mol Pharmacol. 2017 Jan;91(1):58-64. PMID: 27974637
66. Wang Y, Chang J, et al. "Discovery of piperlongumine as a potential novel lead for the development of senolytic agents." Aging (Albany NY). 2016 Nov 19;8(11):2915-2926. PMID: 27913811
67. Nguyen TN, Padman BS, et al. "Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation." J Cell Biol. 2016 Dec 19;215(6):857-874. PMID: 27864321
68. Biskup E, Naym DG, et al. "Small-molecule inhibitors of Ataxia Telangiectasia and Rad3 related kinase (ATR) sensitize lymphoma cells to UVA radiation." J Dermatol Sci. 2016 Dec;84(3):239-247. PMID: 27743911
69. Connolly PF, Fearnhead HO. "DNA-PK activity is associated with caspase-dependent myogenic differentiation." FEBS J. 2016 Oct;283(19):3626-3636. PMID: 27513301
70. Domalaon R, Findlay B, et al. "Ultrashort cationic ipopeptides and lipopeptoids: Evaluation and mechanistic insights against epithelial cancer cells." Peptides. 2016 Jul 30. PMID: 27486068
71. Vasuthasawat A, Yoo EM, et al."Targeted immunotherapy using anti-CD138-interferon α fusion proteins and bortezomib results in synergistic protection against multiple myeloma." MAbs. 2016 Jun 30:0. PMID: 27362935
72. Nogusa S, Thapa RJ, et al. "RIPK3 Activates Parallel Pathways of MLKL-Driven Necroptosis and FADD-Mediated Apoptosis to Protect against Influenza A Virus." Cell Host Microbe. 2016 Jun 15. PMID: 27321907
73. Lazarou, Michael, et al. "The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy." Nature (2015). PMID: 26266977
74. Nezich, Catherine L., et al. "MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5." The Journal of cell biology 210.3 (2015): 435-450. PMID: 26240184
75. Tang, Zijian, et al. "MEK Guards Proteome Stability and Inhibits Tumor-Suppressive Amyloidogenesis via HSF1." Cell 160.4 (2015): 729-744. PMID: 25679764

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Chemical Properties

Storage	Store at -20°C
M.Wt	513.49
Cas No.	1135695-98-5
Formula	C₂₆H₂₅F₂N₃O₆·xH₂O
Solubility	≥25.67 mg/mL in DMSO; insoluble in H2O; ≥28.75 mg/mL in EtOH
Chemical Name	(3S)-5-(2,6-difluorophenoxy)-3-[[(2S)-3-methyl-2-(quinoline-2-carbonylamino)butanoyl]amino]-4-oxopentanoic acid
SDF	Download SDF
Canonical SMILES	CC(C)C(C(=O)NC(CC(=O)O)C(=O)COC1=C(C=CC=C1F)F)NC(=O)C2=NC3=CC=CC=C3C=C2
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment[1]:
Cell lines	JURL-MK1 and HL60 cell
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	No specific suggestion
Applications	Q-VD-OPh largely inhibited caspase-3 and 7 activity at 0.05 mM. Caspase-8 was also inhibited by Q-VD-OPh at very low concentration. Q-VD-OPh prevented the cleavage of PARP-1 at 10 mM . Q-VD-OPh inhibited DNA fragmentation and disruption of the cell membrane functionality at 2 mM, and the drug-induced loss of cellular adhesivity to fibronectin need 10 mM Q-VD-OPh.
Animal experiment [2]:
Animal models	TgCRND8 mice in 3 months-old
Dosage form	Intraperitoneally Injected with 10 mg/kg QVD-OPh at 3 times a week for 3 months
Applications	Q-VD-OPh inhibited caspase-7 activation and limited the pathological changes of tau and caspase cleavage in chronic treatment of Alzheimer disease.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: 1. Kuželová K1, Grebeňová D, Brodská B.Dose-dependent effects of the caspase inhibitor Q-VD-OPh on different apoptosis-related processes. J Cell Biochem. 2011 Nov;112(11):3334-42. 2. Rohn TT, Kokoulina P, Eaton CR et al. Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh. Int J Clin Exp Med. 2009 Nov 5;2(4):300-8.

Biological Activity

Q-VD-OPH is a selective, brain and cell permeable, highly potent and irreversible inhibitor of caspase-3 ( IC50=25nm), caspase-1 (IC50=50nM), caspase-8 (IC50=100nM) and caspase-9 (IC50=430nM).
Targets	caspase-1	caspase-3	caspase-8	caspase-9
IC50	50nM	25nm	100nM	430nM

Quality Control

Purity = 99.84%

Q-VD-OPh [1135695-98-5]

Referência A1901-1mg

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Marca : APExBIO Technology