Panobinostat (LBH-589) is a highly potent hydroxamic acid–derived deacetylase inhibitor shown to impede multiple pathways implicated in cancer, including cell division, hypoxia response, and angiogenesis . It is sometimes given intravenously, but oral formulations are also being tested.
Manufacturer: Novartis Oncology
Information at manufacturer website: link here
Definition from NCI Drug Dictionary: Panobinostat (LBH589) is a cinnamic hydroxamic acid analogue with potential antineoplastic activity. Panobinostat selectively inhibits histone deacetylase (HDAC), inducing hyperacetylation of core histone proteins, which may result in modulation of cell cycle protein expression, cell cycle arrest in the G2/M phase and apoptosis. In addition, this agent appears to modulate the expression of angiogenesis-related genes, such as hypoxia-inducible factor-1alpha (HIF-1a) and vascular endothelial growth factor (VEGF), thus impairing endothelial cell chemotaxis and invasion. HDAC is an enzyme that deacetylates chromatin histone proteins.
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Current Clinical Trials relevant to GIST:
NCT00739414 Dose-escalating Study of LBH589 in Adult Patients With Advanced Solid Tumors
NCT01007968 Pharmacokinetics and Safety of Panobinostat in Patients With Advanced Solid Tumors and Various Degrees of Hepatic Function. Not yet recruiting .
NCT00997399 Study to Evaluate Panobinostat (DACi) Pharmacokinetics and Safety in Solid Tumors and Varying Renal Function. Not yet recruiting
A Phase I trial using a combination of imatinib plus panobinostat is expected to begin recruiting in Germany in December 2009, with Sebastian Bauer MD as the principal investigator.