GPI-16552 (443794-40-9) is a novel potent inhibitor of poly(ADP-ribose) glycohydrolase (PARG), IC50=1.7 μM1. Pre or post ischemia treatment (40 mg/kg) with GPI-16552 reduces brain infarct volumes in a rat model of cerebral ischemia2. It modulates the inflammatory response to ischemia/reperfusion in a rat splanchnic artery occlusion model3 and reduces the degree of spinal cord inflammation and tissue injury after experimental spinal cord trauma4. GPI-16552 synergizes with temozolomide in decreasing melanoma cell invasion and metastatic spreading in mice injected with B16 melanoma cells5.
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2) Lu et al. (2003), Post-treatment with a novel PARG inhibitor reduces infarct in cerebral ischemia in the rat; Brain Res., 978 99
3) Cuzzocrea et al. (2005), PARG activity mediates intestinal injury induced by splanchnic artery occlusion and reprofusion; FASEB J., 19 558
4) Cuzzocrea et al. (2006), Poly(ADP-ribose) glycohydrolase activity mediates post-traumatic inflammatory reaction after experimental spinal cord trauma; J. Pharmacol. Exp. Ther., 319 127
5) Tentori et al. (2005), Poly(ADP-roibose) glycohydrolase inhibitor as chemosensitiser of malignant melanoma for temozolomide; Eur. J. Cancer, 41 2948