| Description: |
Q-VD-OPha is a irreversible pan-caspase inhibitor with potent antiapoptotic properties; inhibits caspase 7 with IC50 of 48 nM and 25-400 nM for other caspases including caspase 1, 3, 8, 9, 10, and 12. Q-VD-OPha is able to cross the blood-brain barrier. |
| Target: |
Caspase-3:25-400 nM (IC50)
Caspase-7:48 nM (IC50)
Caspase-1:25-400 nM (IC50)
Caspase-8:25-400 nM (IC50)
Caspase-9:25-400 nM (IC50)
Caspase-10:25-400 nM (IC50)
Caspase-12:25-400 nM (IC50) |
| In Vivo: |
Chronic treatment with Q-VD-OPh prevents caspase-7 activation and limits the pathological changes associated with tau, including caspase cleavage. Q-VD-OPh could be a potential therapeutic compound for the treatment of Alzheimer's disease[1]. |
| In Vitro: |
Q-VD-OPh is a potent inhibitor of caspase-7 with an IC50 of 48 nM utilizing a cell-free assay consisting of human recombinant caspase-7, Q-VD-OPh, and the substrate AMC-DEVD-pNa[1]. Q-VD-OPh fully inhibits caspase-3 and -7 activity at 0.05 μM. Caspase-8 is also inhibited at low Q-VD-OPh concentrations. The cleavage of PARP-1 is fully prevented at 10 μM Q-VD-OPh. DNA fragmentation and disruption of the cell membrane functionality are both prevented at 2 μM Q-VD-OPh[2]. Q-VD-OPh is significantly more effective in preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk, and is also equally effective in preventing apoptosis mediated by the three major apoptotic pathways, caspase 9/3, caspase 8/10, and caspase12. Q-VD-OPh is not toxic to cells even at extremely high concentrations[3]. QVD is also able to increase the expression of differentiation markers in acute myeloid leukemia (AmL) blasts. QVD alone or combined with VDDs increases differentiation and HPK1-cJun signaling in AmL cell context-dependent manner[4]. |
| Animal Administration: |
Mouse: Stock solutions of Q-VD-OPh are prepared in DMSO and diluted in sterile PBS solution prior to injection. A final concentration of 10 mg/kg is chosen indicating neuroprotection at this concentration of Q-VD-OPh. Three-month old mice are divided into two groups: control, vehicle (n=3) or treated (n=2). Mice are injected i.p. three times a week with either Q-VD-OPh or vehicle for a total time period of 3 months[1]. |
| References: |
[1]. Rohn TT, 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.
[2]. Kuzelová K, et al. Dose-dependent effects of the caspase inhibitor Q-VD-OPh on different apoptosis-related processes. J Cell Biochem. 2011 Nov;112(11):3334-42.
[3]. Caserta TM, et al. Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties. Apoptosis. 2003 Aug;8(4):345-52.
[4]. Chen-Deutsch X, et al. Leuk Res. 2012 Jul;36(7):884-8.The pan-caspase inhibitor Q-VD-OPh has anti-leukemia effects and can interact with vitamin D analogs to increase HPK1 signaling in AML cells. |
