P-3703 Panobinostat, Free Base, >99%

Related Terms : [Faridak] [LBH-589] [NVP-LBH-589]

Note: Our Euro, Pound, and Yen prices are revised regularly to account for currency exchange rate fluctuations.

To receive a full, detailed quotation for catalog sizes of this product and/or any other products load them into your shopping cart, then view your cart and select the appropriate option.

  • M.W. 349.43
  • C21H23N3O2
  • [404950-80-7]

Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 200 mg/mL; soluble in ethanol at 5 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 20-50 µM buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A.

  • 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. Qian, D.Z., et al. "Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589." Clin. Cancer Res. 12: 634-642 (2006).
  • 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. Haefner, M., et al. "Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors." World J. Gastroenterol. 14: 3681-3692 (2008).
  • 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. George, P., et al. "Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3." Blood 105: 1768-1776 (2005).
  • 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). Maiso, P., et al. "The histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance." Cancer Res. 66: 5781-5789 (2006).
  • Panobinostat is well tolerated and induces clinical responses in cutaneous T-cell lymphoma (CTCL) patients. Ellis, L., et al. "Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma." Clin. Cancer Res. 14: 4500-4510 (2008).
  • QTcF prolongation was one of the dose-limiting toxicities of panobinostat but was asymptomatic and was reversed after panobinostat discontinuation. Giles, F., et al. "A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies." Clin. Cancer Res. 12: 4628-4635 (2006).
  • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.
  • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
  • Not available in some countries; not available to some institutions; not available for some uses.
219