Panobinostat, Free Base (Faridak, LBH-589, NVP-LBH-589, CAS 404950-80-7), >99%

LC Laboratories' Product Number P-3703 - Panobinostat, Free Base (Faridak, LBH-589, NVP-LBH-589, CAS 404950-80-7), >99% - for research use only. Panobinostat, a histone deacetylase inhibitor, is being tested in humans against cutaneous T cell lymphoma, prostate cancer, myelodysplastic syndromes, breast cancer, chronic myelogenous leukemia, and other types of malignant disease. Panobinostat inhibited histone deacetylase and induced acetylation of histone H3 and alpha-tubulin protein in human umbilical vein endothelial cells (HUVEC), which resulted in induction of G(2)-M cell cycle arrest and inhibition of HUVEC proliferation and viability. Panobinostat at noncytotoxic concentrations inhibited endothelial tube formation, Matrigel invasion, AKT activity, extracellular signal-regulated kinase 1/2 phosphorylation and chemokine receptor CXCR4 expression. It aslo reduced angiogenesis and PC-3 tumor growth in mice. After 3 days of incubation, panobinostat inhibited the proliferation of 7 of 8 tested pancreatic cell lines with a mean IC50 of 0.09 µM. Only cell line Capan-2 demonstrated an IC50 value >1 µM. Inhibition of cell growth was more marked if the incubation time was extended to 6 days. In vivo, panobinostat alone significantly decreased tumor mass and augmented the efficacy of gemcitabine. In addition to acetylation of histone H3 and H4, panobinostat also induces acetylation of heat shock protein 90 (hsp90). Cotreatment with panobinostat and the hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, Cat. No. A-6880) caused synergistic apoptosis of acute leukemia MV4-11 and K562 cells. This combination treatment induced apoptosis of the imatinib mesylate (IM)-refractory leukemia cells expressing Bcr-Abl with the T315I mutation. The cotreatment also brought about more apoptosis of IM-resistant primary chronic myeloid leukemia blast crisis (CML-BC) and acute myeloid leukemia (AML) cells with an activating mutation of FLT-3 than treatment with either drug alone. Treatment with LBH589 for 48 hours potently inhibited MTT uptake. IC50 values for these multiple myeloma cell lines were 5.7 nM (MM1S), 6.5 nM (MM1R), 8.1 nM (U266), 24 nM (U266LR7), and 45.5 nM (U266DOX4). Panobinostat is well tolerated and induces clinical responses in cutaneous T-cell lymphoma (CTCL) patients. QTcF prolongation was one of the dose-limiting toxicities of panobinostat but was asymptomatic and was reversed after panobinostat discontinuation.

• Supplier: LC Laboratories
• Product #: P-3703
• Sku #: P-3703_1g