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P-3703 Panobinostat, Free Base, >99%

[Faridak] [LBH-589] [NVP-LBH-589] [LBH 589] [LBH589]

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

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View the MSDS for this product

• 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.

** Our prices are lower than other vendors', but there is no compromise in quality.  Read how we are able to accomplish this:  Product Quality Discussion.

NOTES:
1.  The purpose of our competitor price comparison tables is to enable our visitors to compare the prices and purities of products of nominally equivalent quality, for vendors whose price and purity claims are openly available from a website or catalog (without a need for the customer to contact the vendor and request a quotation in order to obtain a price and purity for a standard product size).  However, the quality comparisons in these tables are not absolute:  although our product purities are uniformly very high and are established by careful testing of every lot in our laboratories, we cannot and do not vouch for the purities claimed by other vendors in these competitor price comparison tables.  (We do carry out occasional testing of other vendors' products -- see below --  and we have found many instances where vendors' product purities are far below their claimed levels.)  Effective April 1, 2011, our price comparison tables only include products where a purity commitment is found together with sizes and prices on at least one page of the vendor's web site.

2.  Researching and compiling sizes and prices for the >160 competitive vendors and more than 175 products is an expensive and tedious task for our small company.  Thus, we typically only perform revisions of these tables annually or less frequently.  The date and source of each competitive vendor's prices is indicated at the bottom of this page.  Obviously, we make no guarantee that competitive vendor prices will remain unchanged in the interval between our annual revisions.  We may occasionally update individual competitive vendor information and add new competitive vendors as we locate them.

3.  In some circumstances we permanently remove vendors from our price comparison tables.  Circumstances that lead to permanent removal are: 

A.  If a vendor does not honor its advertised price (ignoring small price increases) for one or more products when an order is attempted.  Example:  a vendor listed a compound at $808 for 10 grams on its website price list, but quoted $4,500 per 10 grams upon our inquiry.  That vendor has been permanently removed from our price comparison tables.

B.  If, on a product-by-product basis, our analyses of a vendor's product show purities more than a few percent below the vendor's advertised purities.  Example:  a vendor advertises a purity for 97% for a compound, but repeated elemental analyses show a minimum of 9% inorganic material present, beyond any salt counterion.  Another example: an HPLC analysis at a relevant UV detector wavelength shows 92% purity for a vendor's product for which 98% purity is claimed.  We realize of course that UV absorbances for impurities can be higher than for the main compound, but our products meet our purity commitment of typically >99% irrespective of absorbance factors for impurities, and we apply that standard to products from other vendors.

C.  Again on a product-by-product basis, if a vendor makes no purity claim for a given product, then their product is not shown on that product table.

D.  If we find that, as a pattern, several of a competitive vendor's products fail to meet their advertised purity commitments by significant margins or if a vendor does not provide standard and consistent purity claims for several of its products, then that vendor is permanently removed from all of our competitor price tables.

E.  Finally, if we determine that a vendor has provided fraudulent information on its website, in its literature or on a certificate of analysis, that vendor is permanently removed from all of our price comparison tables.

4.  IMPORTANT:  The presence of a competitive vendor entry in our price comparison tables does not necessarily mean that we have analyzed any of that vendor's products for purity; indeed, in most cases we have not.

5.  Please note:  where necessary, competitor prices are rounded to the nearest whole dollar.

To the best of our knowledge, the prices listed above for our competitors' products were correct as of the dates listed below for the sources of our annual price information update process.

Pricing Sources and Dates:  LC Labs - Current, AG Scientific - website - Jan 2013, Santa Cruz Biotech - website - Jan 2013, Active Biochem - website - Mar 2013, US Biological - website - Mar 2013, BioVision - website - Jan 2013, D-L Chiral Chemicals - website - Jan 2013, PharmBlock - website - Apr 2013, BePharm - website - May 2013, Cambridge BioScience - website - Oct 2012, ChemieTek - website - Dec 2012, Axon Medchem - website - May 2013, JiHe Pharmaceutica - website - Jan 2013, VDM Biochemicals - website - Dec 2012, antibodies-online - website - Jan 2013, biorbyt.com - website - Jan 2013, Reagents Direct - website - Dec 2012, biokits.com - website - Jan 2013, HuoLi Biochem - website - Nov 2012, Acesobio - website - Jan 2013, Cellagen Technology - website - Mar 2013, P212121 - website - Oct 2012, AbMole BioScience - website - Dec 2012, MedKoo BioSciences - website - Apr 2013, Ark Pharm - website - Dec 2012, Medchem Express - website - Jan 2013, AdooQ BioScience - website - Jan 2013, ChemScene - website - Jan 2013, Kinasechem - website - Apr 2013.