Panobinostat

Panobinostat is a potent pan-histone deacetylase (HDAC) inhibitor (IC₅₀ values = 2.1 - 531 nM). Panobinostat induces histone H3 and H4 acetylation and potently inhibits cell proliferation and cell viability in HH, BT474 and HCT116 cells (IC₅₀ are 1.8, 2.6 and 7.1 nM, respectively) in vitro. It leads to significant tumor regression of up to 94% in an HH CTCL mouse xenograft model. Panobinostat inhibits the DNA binding activity of STAT5 in leukemia cell lines and acts synergistically with 17-AAG (Cat. No. 1515) to induce apoptosis. The compound shows potent antimyeloma activity, including in drug-resistant cell lines. Panobinostat also induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4⁺ T cells and leads to activation of transcription of proviruses. Panobinostat simultaneously suppresses the expression of angiotensin-converting enzyme 2 (ACE2) and ABO in epithelial cell lines. Antimalarial and orally bioavailable.