Histone Deacetylase Inhibitors

Histone deacetylase inhibitors (HDAC or HDACIs) are an emerging class of anticancer agents with demonstrable preclinical antitumor activity in both in vitro and in vivo studies in a wide range of malignancies.

Based on these preclinical findings, in recent years HDACIs have undergone a rapid phase of clinical development with many HDACIs entering Phase I–III clinical trials, both as single agents and in combination with other therapies.

In fact, several compounds in this class, including Suberoylanilide hydroxamic acid (SAHA), MS-27-275, BML-210, M344 and CI-994, are currently undergoing clinical trials.

At the moment we can offer you the following HDAC inhibitors from stock: Suberoylanilide Hydroxamic Acid (SAHA); Entinostat (MS-275); Tacedinaline (CI-994); BML-210; M344; Mocetinostat (MGCD0103); Belinostat (PXD101); Panobinostat (LBH-589).

All these compounds are in stock and can be delivered in 5-10 days. The minimum purity of HDAC inhibitors is 97%. H1NMR and LCMS analytical data are available upon request.

Suberoylanilide Hydroxamic Acid

Synonyms: N1-hydroxy-N8-phenyl-octanediamide; SAHA; Vorinostat; Zolinza; Octanedioic acid hydroxyamide phenylamide
Technical Data: Molecular Weight - 264.33; Molecular formula - C14H20N2O3; CAS No - 149647-78-9

SAHA inhibits class I and class II HDACs at nanomolar concentrations and arrests cell growth in a wide variety of transformed cells in culture at 2.5-5.0 µM. This compound efficiently suppressed MES-SA cell growth at a low dosage (3 µM) already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 µM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours.

References:
1. Marks, P.A., Breslow, R. Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotech 25(1) 84-90 (2007). DOI: 10.1038/nbt1272
2. Takashi Kumagai, et al. Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells. International Journal of Cancer. 2007 Aug 1;121(3):656-65. DOI: 10.1002/ijc.22558
3. Hrzenjak A, et al. Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo. Mol Cancer. 2010 Mar 4;9:49. DOI: 10.1186/1476-4598-9-49

Ordering Information: Product Number - EC-000.2057; Price and Availability: Inquire

Entinostat

Synonyms: SNDX-275; MS-275; MS-27-275; Entinostat; pyridin-3-ylmethyl 4-(2-aminophenylcarbamoyl)benzylcarbamate
Technical Data: Molecular Weight - 376.42; Molecular formula - C21H20N4O3; CAS No - 209783-80-2

Entinostat (MS-275) preferentially inhibits HDAC1 (IC50=300nM) over HDAC3 (IC50=8µM) and has no inhibitory activity towards HDAC8 (IC50>100µM). MS-275 induces cyclin-dependent kinase inhibitor 1A (p21/CIP1/WAF1), slowing cell growth, differentiation, and tumor development in vivo. Recent studies suggest that MS-275 may be particularly useful as an antineoplastic agent when combined with other drugs, like adriamycin.

References:
1. Saito, A. et al. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci USA 96 4592-4597 (1999).
2. Jaboin, J., et al. MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors. Cancer Res 62 6108-6115 (2002).
3. Rosato RR, et al. The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. Cancer Res 2003; 63: 3637–3645.

Ordering Information: Product Number - EC-000.2117; Price and Availability: Inquire

Tacedinaline

Synonyms: CI-994; PD-123654; GOE-5549; Acetyldinaline; 4-Acetamido-N-(2-aminophenyl)benzamide
Technical Data: Molecular Weight - 269.31; Molecular formula - C15H15N3O2; CAS No - 112522-64-2

CI-994 (Acetyldinaline) is an anti-cancer drug which inhibits histone deacetylases. In vitro, CI-994 in combination with cytarabine (ara-C), daunorubicin and mitoxantrone, resulted in moderate synergism. In vivo, higher dosages of CI-994 induced complete remissions. CI-994/ara-C was very active against BNML (Brown Norway rat acute myelocytic leukemia). The combinations of CI-994/daunorubicin and CI-994/mitoxantrone were also active against BNML.

References:
1. Hubeek I, et al. CI-994 (N-acetyl-dinaline) in combination with conventional anti-cancer agents is effective against acute myeloid leukemia in vitro and in vivo. Oncol Rep. 2008 Jun;19(6):1517-23.
2. Loprevite M, et al. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines. Oncol Res. 2005;15(1):39-48.
3. Kouraklis G, et al. Histone deacetylase inhibitors: a novel target of anticancer therapy (review). Oncol Rep. 2006 Feb;15(2):489-94.

Ordering Information: Product Number - EC-000.2116; Price and Availability: Inquire

BML-210

BML-210 is a small molecule inhibitor of HDAC with an IC50 value of 30 µM when tested in HeLa cell nuclear extracts using 200 µM acetylated fluorometric substrate. This compound also inhibits the deacetylation of the transcription factor FOXO3 by mammalian SIRT1 in cells oxidatively stressed by hydrogen peroxide.

Synonyms: BML 210; N-(2-aminophenyl)-N'-phenyl-octanediamide
Technical Data: Molecular Weight - 339.44; Molecular formula - C20H25N3O2; CAS No - 537034-17-6

References:
1. Yoshida, M., et al. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265(28) 17174-17179 (1990).
2. Savickiene J, et al. The novel histone deacetylase inhibitor BML-210 exerts growth inhibitory, proapoptotic and differentiation stimulating effects on the human leukemia cell lines. Eur J Pharmacol. 2006 Nov 7;549(1-3):9-18.
3. Brunet, A., et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303 2011-2015 (2004).

Ordering Information: Product Number - EC-000.2274; Price and Availability: Inquire

M344

M344 is an inhibitor of histone deacetylases, inhibiting maize HDAC (IC50 = 100 nM) as well as human HDAC1 (IC50 = 46 nM). It shows a three-fold selectivity for inhibition of HDAC6 over HDAC1. This compound enhances the sensitivity of human squamous carcinoma cells to radiation and promotes cell cycle arrest and apoptosis in human endometrial cancer and ovarian cancer cells (ED50 = 2.3 µM).

Synonyms: M 344; D237; 4-Dimethylamino-N-(6-hydroxycarbamoylhexyl)-benzamide
Technical Data: Molecular Weight - 307.40; Molecular formula - C16H25N3O3; CAS No - 251456-60-7

References:
1. Zhang, Y., et al. Enhancement of radiation sensitivity of human squamous carcinoma cells by histone deacetylase inhibitors. Radiat Res 161 667-674 (2004).
2. Shabason JE, et al. HDAC inhibitors in cancer care. Oncology (Williston Park). 2010 Feb;24(2):180-5.
3. Takai, N., et al. M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells. Gynecol Oncol 101 108-113 (2006).

Ordering Information: Product Number - EC-000.2275; Price and Availability: Inquire

MGCD0103

MGCD0103 inhibits class 1 isoforms of HDAC, specifically HDAC1 (IC50=0.15 µM), HDAC2 (IC50=0.29 µM) and HDAC3 (IC50=1.66 µM), which may result in epigenetic changes in tumor cells and so tumor cell death. It exhibited potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines (IC50 from 0.09-20 µM) in vitro, and HDAC inhibitory activity was required for these effects. In vivo, MGCD0103 significantly inhibited growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors.

Synonyms: MGCD-0103; Mocetinostat
Technical Data: Molecular Weight - 396.46; Molecular formula - C23H20N6O; CAS No - 726169-73-9

References:
1. Chia K, et al. The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity. Mol Pharmacol. 2010 Jun 10.
2. Prince HM, et al. Clinical studies of histone deacetylase inhibitors. Clin Cancer Res. 2009 Jun 15;15(12):3958-69.
3. Marielle Fournel, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther 2008;7(4).

Ordering Information: Product Number - EC-000.2284; Price and Availability: Inquire

Belinostat

PXD101 (Belinostat) is a novel hydroxamate-type inhibitor of histone deacetylase activity. It inhibits HDAC activity in HeLa cell extracts with an IC50 of 27 nM. PXD101 is cytotoxic in vitro in a number of tumor cell lines with IC50s in the range 0.2-3.4 µM as determined by a clonogenic assay and induces apoptosis. This hdac inhibitor is currently under phase I/II testing in lymphoma, ovarian cancer and other solid tumors.

Synonyms: PXD101; PX105684; (E)-N-hydroxy-3-(3-(N-phenylsulfamoyl)phenyl)acrylamide
Technical Data: Molecular Weight - 318.35; Molecular formula - C15H14N2O4S; CAS No - 414864-00-9

References:
1. Plumb JA, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8.
2. Zain JM, et al. Targeted treatment and new agents in peripheral T-cell lymphoma. Int J Hematol. 2010 Jun 10.
3. Ramalingam SS, et al. Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J Thorac Oncol. 2009 Jan;4(1):97-101.

Ordering Information: Product Number - EC-000.2286; Price and Availability: Inquire

Panobinostat

LBH589, a novel hydroxamate analog HDAC inhibitor, has been shown to induce acetylation of histone H3 and H4, increase p21 levels, disrupt the chaperone function of hsp90, and induce cell-cycle G1 phase accumulation and apoptosis of K562 cells and acute leukemia MV4-11 cells. The anti-tumor effect by LBH589 was also demonstrated in multiple myeloma, NSCLC as well as castrate-resistant prostate cancer cell lines.

Synonyms: LBH-589; LBN-589; LBH589; NVP-LBH589
Technical Data: Molecular Weight - 349.44; Molecular formula - C21H23N3O2; CAS No - 404950-80-7

References:
1. Tan J, et al. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol. 2010 Feb 4;3:5.
2. Chen S, et al. The HDAC inhibitor LBH589 (panobinostat) is an inhibitory modulator of aromatase gene expression. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11032-7.
3. Minucci S, et al. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006 Jan;6(1):38-51.

Ordering Information: Product Number - EC-000.2287; Price and Availability: Inquire

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