Panobinostat

Danger

H301+H331 (97.2%): Toxic if swallowed or if inhaled [Danger Acute toxicity, oral; acute toxicity, inhalation]

P203, P260, P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P354+P338, P316, P317, P318, P319, P321, P330, P332+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 71 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Most clinical trials of panobinostat have not reported rates of serum enzyme elevations during therapy and it is typically given in combination with other antineoplastic agents that can cause serum ALT and AST elevations. In the large controlled trial of panobinostat vs placebo in combination with bortezomib and dexamethasone, ALT elevations occurred in similar proportion of patients receiving panobinostat (31%) as placebo (38%) and values above 5 times the upper limit of normal were uncommon (1.8% and 1.3%). In addition, there have been no reports of clinically apparent liver injury with jaundice associated with panobinostat therapy. Thus, panobinostat appears to have little hepatotoxic potential and liver injury from panobinostat must be quite rare, if it occurs at all.

L01XX42

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Panobinostat is a deacetylase (DAC) inhibitor. DACs, also known as histone DACs (HDAC), are responsible for regulating the acetylation of about 1750 proteins in the body; their functions are involved in many biological processes including DNA replication and repair, chromatin remodelling, transcription of genes, progression of the cell-cycle, protein degradation and cytoskeletal reorganization. In multiple myeloma, there is an overexpression of DAC proteins. Panobinostat inhibits class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC 11) proteins. Panobinostat's antitumor activity is believed to be attributed to epigenetic modulation of gene expression and inhibition of protein metabolism. Panobinostat also exhibits cytotoxic synergy with bortezomib, a proteasome inhibitor concurrently used in treatment of multiple myeloma.

Panobinostat was extensively metabolized to 77 metabolites. Unchanged panobinostat recovered in urine and feces was 2% and 3%, respectively. Primary metabolic pathways of panobinostat are reduction, hydrolysis, oxidation, and glucuronidation processes. CYP and non-CYP enzymes were found to play significant role in metabolism, CYP2D6 and CYP2C19 playing minor roles.

9647FM7Y3Z

histone deacetylase (HDAC) inhibitor

Established Pharmacologic Class [EPC] - Histone Deacetylase Inhibitor

Mechanisms of Action [MoA] - Histone Deacetylase Inhibitors

Mechanisms of Action [MoA] - Cytochrome P450 2D6 Inhibitors

Histone deacetylase (hdac) inhibitor is a Histone Deacetylase Inhibitor. The mechanism of action of histone deacetylase (hdac) inhibitor is as a Histone Deacetylase Inhibitor and Cytochrome P450 2D6 Inhibitor.