panobinostat + pemetrexed

Panobinostat (LBH589) is a potent, orally available pan-histone deacetylase (HDAC) inhibitor that targets Class I, II, and IV HDAC enzymes. Developed by Novartis, it is marketed as Farydak for multiple myeloma. Its mechanism involves increasing the acetylation of histones and non-histone proteins, which modulates gene expression to induce cell cycle arrest and apoptosis in cancer cells. In a clinical research program led by the University of Pittsburgh, panobinostat is being investigated in combination with pemetrexed (Alimta), a multi-targeted antifolate developed by Eli Lilly. Pemetrexed inhibits several enzymes involved in folate metabolism, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GART). The combination therapy aims to exploit the ability of HDAC inhibitors to downregulate TS expression, thereby enhancing the sensitivity of non-small cell lung cancer (NSCLC) cells to pemetrexed-mediated cytotoxicity.

Brand names

FarydakAlimta

Other names

LBH 589LBH589LBH-589