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Q-VD-OPH, A new generation broad spectrum Caspase Inhibitor QVDOPH is a non- FMK new generation broad spectrum inhibitor that offers improvement in potency, stability and toxicity over the bench mark caspase inhibitor Z-VAD-FMK. Q-VD-OPH doesn’t cross reacts with cathepsins or calpains and FMK (Fluoromethyl Ketones) does. The improvements derive from significant changes that include replacement of the carbobenzoyloxy blocking group (Z) with a Quinoline derivative (Q), modification of the tripeptide sequence from VAD to VD, and replacement of fluoromethyl ketone (FMK) with the non toxic 2,6-difluorophenoxy methyl (OPH) group. The mechanism of action involves the formation of an irreversible thioether bond between the aspartic acid derivative in the inhibitor and the active site cysteine with displacement of 2,6-difluorphenoxy group. Q-VD-OPH is a small hydrophobic compound . Therefore, DMSO is required for solubilization. Stock solutions as high as 200 mg / ml have been prepared in DMSO. To retain solubility in water at concentrations above 1 mg / ml, 80 % DMSO is suggested. Q-VD-OPH is effective in vitro at concentrations of 10uM to 20uM. For tissue culture studies 10mM or 20mM stock solutions are prepared in DMSO and diluted 1:1000 directly into the tissue culture medium. For studies in vivo Q-VD-OPH has been administered in 80% to 100% DMSO to assure solubility at the doses given. A dose of 20mg/Kg has been used most frequently. Q-VD-OPH has been shown to inhibit recombinant Caspases 2, 3, 8 and 9 with IC50 values ranging from 25 to 400 nM. A preliminary acute toxicity screen was done in which mice were injected IP with 200 mg/kg, 500 mg/kg or 1000 mg /kg in 100 % DMSO. Mice were sacrificed and autopsied 24 hours later. No gross pathologies were seen and no evidence of toxicity was observed in histological sections from major organs. Q-VD-OPH, A new generation broad spectrum Caspase Inhibitor Q-VD-OPH is a non- FMK new generation broad spectrum inhibitor that offers improvement in potency, stability and toxicity over the bench mark caspase inhibitor Z-VAD-FMK. Q-VD-OPH doesn’t cross reacts with cathepsins or calpains and FMK (Fluoromethyl Ketones) does. The improvements derive from significant changes that include replacement of the carbobenzoyloxy blocking group (Z) with a Quinoline derivative (Q), modification of the tripeptide sequence from VAD to VD, and replacement of fluoromethyl ketone (FMK) with the non toxic 2,6-difluorophenoxy methyl (OPH) group. The mechanism of action involves the formation of an irreversible thioether bond between the aspartic acid derivative in the inhibitor and the active site cysteine with displacement of 2,6-difluorphenoxy group. Q-VD-OPH is a small hydrophobic compound . Therefore, DMSO is required for solubilization. Stock solutions as high as 200 mg / ml have been prepared in DMSO. To retain solubility in water at concentrations above 1 mg / ml, 80 % DMSO is suggested. Q-VD-OPH is effective in vitro at concentrations of 10uM to 20uM. For tissue culture studies 10mM or 20mM stock solutions are prepared in DMSO and diluted 1:1000 directly into the tissue culture medium. For studies in vivo Q-VD-OPH has been administered in 80% to 100% DMSO to assure solubility at the doses given. A dose of 20mg/Kg has been used most frequently. Q-VD-OPH has been shown to inhibit recombinant Caspases 2, 3, 8 and 9 with IC50 values ranging from 25 to 400 nM.

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