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).¹It 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 IC₅₀values 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)