GPI-16552 (443794-40-9) is a novel potent inhibitor of poly(ADP-ribose) glycohydrolase (PARG), IC50=1.7 μM.1 Pre or post ischemia treatment (40 mg/kg) with GPI-16552 reduces brain infarct volumes in a rat model of cerebral ischemia.2?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 cells.5
1) Zhang?et al. (2002),?PARP and PARG as novel therapeutic targets; Drugs Future,?27?371
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 reperfusion; 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-ribose) glycohydrolase inhibitor as chemosensitiser of malignant melanoma for temozolomide; Eur. J. Cancer,?41?2948
