CP-461

CP-461 (also known as OSI-461) is a small molecule selective apoptotic antineoplastic drug (SAAND) and a second-generation derivative of exisulind. It acts as a potent inhibitor of cGMP-specific phosphodiesterases (PDE), which leads to increased intracellular cGMP levels and the activation of protein kinase G (PKG). This signaling cascade induces apoptosis in cancer cells through the activation of JNK and the induction of pro-apoptotic genes such as mda-7/IL-24 and GADD45. Developed initially by Cell Pathways and later by OSI Pharmaceuticals (acquired by Astellas Pharma), CP-461 was evaluated in Phase II clinical trials for various malignancies, including melanoma, prostate cancer, renal cell carcinoma, and chronic lymphocytic leukemia, as well as for inflammatory conditions like Crohn's disease. Clinical development was largely discontinued after early-phase studies showed limited monotherapy efficacy.

Other names

exisulind analogZ-5-fluoro-2-methyl-(4-pyridylidene)-3-(N-benzyl)-indenylacetamide hydrochloride