A dual inhibitor of PARP and PI3K
CAY10749 is a dual inhibitor of poly(ADP-ribose) polymerase (PARP) and PI3K (IC50s = 6.03, 3.63, 5.62, and 7.41 nM for PARP1, PARP2, PI3Kα, and PI3Kδ, respectively).1 It is selective for these enzymes over PI3Kβ and PI3Kγ (IC50s = 288.4 and 831.76 nM, respectively), as well as a panel of 374 additional kinases at 1 µM. CAY10749 (1 µM) induces dsDNA break formation in a neutral comet assay and apoptosis in MDA-MB-468 breast cancer cells. It inhibits proliferation of eight cancer cell lines, including pancreatic, ovarian, lymphoma, leukemia, and lung cancer cells, with IC50 values ranging from 398.11 to 2,818.38 nM. CAY10749 (50 mg/kg twice per day) reduces tumor growth by 73.4% in an MDA-MB-468 mouse xenograft model.
1.Wang, J., Li, H., He, G., et al.Discovery of novel dual poly(ADP-ribose)polymerase (PARP) and phosphoinositide 3-kinase (PI3K) inhibitors as a promising strategy for cancer therapyJ. Med. Chem.63(1)122-139(2019)
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