HDAC (pan-inhibitor; class I, II, and IV histone deacetylases). The hydroxamic acid group chelates the catalytic zinc ion in the HDAC active site, blocking deacetylation of histone and non-histone substrates.

Panobinostat lactate causes apoptosis in both MOLT-4 and Reh cells in a time and dose-dependent manner. Panobinostat lactate causes histone (H3K9 and H4K8) hyperacetylation and regulates cell-cycle regulatory genes in Reh cells[1]. shows significant antiproliferative action in human NSCLC cell lines, with IC50 values ranging from 5 to 100 nM [2].

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Panobinostat inhibits HDAC activity at nanomolar concentrations and activates the p21 promoter. It induces hyperacetylation of core histone proteins and exhibits antiproliferative and pro-apoptotic activity against multiple myeloma and other cancer cell lines. Clinical efficacy is established in combination with bortezomib and dexamethasone.

In vivo models of tumor growth produced from Meso and NSCLC cells are markedly inhibited by panobinosta lactate (10, 20 mg/kg, ip). The acetylation of histones H3 and H4 in H69 human SCLC cells derived from SCID mice is significantly elevated by panobinosta lactate [2]. In a disseminated multiple myeloma mouse model, panobinostat lactate (5, 10 and 20 mg/kg ip) clearly shows benefits for lower tumor burden, greatly improves TTE, and minimizes bone density loss[3].

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Panobinostat lactate is clinically approved for multiple myeloma. In animal models, panobinostat demonstrates antitumor activity in hematologic and solid tumor xenografts, with histone acetylation serving as a pharmacodynamic marker. Its in vivo pharmacokinetics and tolerability are well characterized in both preclinical and clinical settings.

In vitro HDAC enzyme assays use fluorogenic acetylated lysine substrates with recombinant HDAC or nuclear extracts. Compound is serially diluted and pre-incubated before substrate addition, and deacetylation is quantified by fluorescence. IC50 values are derived from dose-response curves.

In vitro cell-based assays use multiple myeloma cell lines (e.g., RPMI 8226, MM.1S) treated with serial dilutions of panobinostat for 24–72 hours. Viability is measured by CTG or MTT, histone acetylation is assessed by Western blotting, and apoptosis is quantified by flow cytometry.

Dissolved in Dextrose 5% in water; 10 mg/kg, 20 mg/kg; i.p. injectionsSevere combined immunodeficiency (SCID) mice with M30 (107 cells) or A549 (5 × 106 cells), H69 (2.5 × 106 cells), BK-T (6.5 × 106), H526 (10 × 106), and RG1 (10 × 106) cells

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In vivo animal experiments use multiple myeloma xenografts or syngeneic models. Panobinostat is administered intraperitoneally or orally at doses guided by pharmacokinetic studies. Antitumor efficacy is assessed by tumor volume and survival, with pharmacodynamic analysis of histone acetylation in tumor tissue and bone marrow.

[1]. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood. 2008 May 15;111(10):5093-100.

[2]. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31.

[3]. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica. 2010 May;95(5):794-803.

[4]. Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification. Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11138-E11147.

[5]. Broad activation of latent HIV-1 in vivo. Nat Commun. 2016;7:12731. Published 2016 Sep 8.

Panobinostat lactate is a lactate salt with the counterion of Panobinostat (1+). It is a histone deacetylase inhibitor, often used in combination with bortezomib and dexamethasone to treat multiple myeloma. It has multiple functions, including as an EC 3.5.1.98 (histone deacetylase) inhibitor, an antitumor drug, and an angiogenesis modulator. It is a lactate and organic ammonium salt containing the Panobinostat (1+) ion. Panobinostat has been approved by the U.S. Food and Drug Administration (FDA) under the brand name Farydak for the treatment of certain types of cancer. Currently, Panobinostat is being investigated as an investigational drug in a strategy aimed at curing HIV infection. As an investigational HIV therapy, Panobinostat belongs to a class of drugs known as latency reversal agents. Panobinostat lactate is the lactate form of Panobinostat, a pan-histone deacetylase (HDAC) inhibitor with potential antitumor activity. Following administration of pabisostat, it selectively targets, binds to, and inhibits HDAC, thereby inducing excessive acetylation of core histones. The accumulation of highly acetylated histones leads to chromatin remodeling, altered gene expression patterns, transcriptional repression of tumor oncogenes, and selective transcription of tumor suppressor genes. This ultimately results in inhibition of tumor cell division and induction of tumor cell apoptosis. HDAC (histone deacetylases) are upregulated in various tumor cell types and are enzymes capable of deacetylifying histones.
See also: Pabisostat (with active moiety).

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Drug Indications
Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have previously received at least two prior treatment regimens containing bortezomib and an immunomodulatory agent. Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have previously received at least two prior treatment regimens containing bortezomib and an immunomodulatory agent.

C24H29N3O5

439.50416636467

439.211

960055-56-5

Panobinostat;404950-80-7

23725423

White to off-white solid powder

4.01

138.17

6

6

8

32

533

0

O=C(/C=C/C1C=CC(=CC=1)CNCCC1=C(C)NC2C=CC=CC1=2)NO.OC(C(=O)O)C

XVDWNSFFSMWXJJ-ASTDGNLGSA-N

InChI=1S/C21H23N3O2.C3H6O3/c1-15-18(19-4-2-3-5-20(19)23-15)12-13-22-14-17-8-6-16(7-9-17)10-11-21(25)24-26;1-2(4)3(5)6/h2-11,22-23,26H,12-14H2,1H3,(H,24,25);2,4H,1H3,(H,5,6)/b11-10+;

(E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide;2-hydroxypropanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~227.5 mM; with ultrasonication)

Solubility in Formulation 1: ≥ 5 mg/mL (11.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 5 mg/mL (11.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 5 mg/mL (11.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 900 μL of corn oil and mix well.

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 (Please use freshly prepared in vivo formulations for optimal results.)