Panobinostat: The Small Molecule Metalloenzyme Inhibitor with Marvelous Anticancer Activity.
Histone acetyl transferases (HATs) and histone deacetylases (HDACs) are antagonistic enzymes regulating the turnover of histone acetylation thereby governing gene expression in a precise manner. Histone acetylation deregulation caused by aberrant expression of classical HDACs plays a crucial role in tumour onset and progression making these enzymes as striking targets for anticancer drugs and therapy. Small molecule inhibitors targetting HDACs (HDACi) have shown multiple biological effects including cell cycle arrest, differentiation and apoptosis in cancer cell models. The current review deals with the recently approved pan-HDAC inhibitor panobinostat (LBH589) and its antiproliferative activity against distinct cancers (breast, ovarian, lung and multiple myeloma). The intricate details about the different mechanisms triggered by panobinostat to exert cytotoxic effect in these cancers have also been provided. The article also highlights the different combination strategies of panobinostat which can be utilized for overcoming conventional therapy resistant cases and for achieving the enhanced therapeutic benefit from this marvelous inhibitor in the upcoming future.
Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical & Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India. Shabir.muntazir82@gmail.com.
Shabir Ahmad
SA
Ganai
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077767:Panobinostat; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D054852:Small Molecule Libraries; D000077767:Panobinostat; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases