Dacinostat
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MedKoo CAT#: 200845

CAS#: 404951-53-7

Description: Dacinostat, also known as LAQ824, is a hydroxamate histone deacetylase inhibitor with potential anticancer activity. LAQ824 sensitized nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. LAQ824 reduced clonogenic survival of the H23 and H460 cell lines five-fold compared with controls and four-fold compared with either agent alone (P<0.001). In phase I trials, LAQ824 was well tolerated at doses that induced accumulation of histone acetylation, with higher doses inducing changes consistent with HSP90 inhibition.


Chemical Structure

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Dacinostat
CAS# 404951-53-7

Theoretical Analysis

MedKoo Cat#: 200845
Name: Dacinostat
CAS#: 404951-53-7
Chemical Formula: C22H25N3O3
Exact Mass: 379.18959
Molecular Weight: 379.45
Elemental Analysis: C, 69.64; H, 6.64; N, 11.07; O, 12.65

Price and Availability

Size Price Availability Quantity
50.0mg USD 250.0 2 Weeks
100.0mg USD 450.0 2 Weeks
200.0mg USD 750.0 2 Weeks
500.0mg USD 1550.0 2 Weeks
1.0g USD 2650.0 2 Weeks
2.0g USD 4250.0 2 Weeks
5.0g USD 5950.0 2 Weeks
10.0g USD 9650.0 2 Weeks
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Synonym: NVP-LAQ824; NVP LAQ824; LAQ-824; LAQ824; LAQ 824; Dacinostat.

IUPAC/Chemical Name: (2E)-N-hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide

InChi Key: BWDQBBCUWLSASG-MDZDMXLPSA-N

InChi Code: InChI=1S/C22H25N3O3/c26-14-13-25(12-11-19-15-23-21-4-2-1-3-20(19)21)16-18-7-5-17(6-8-18)9-10-22(27)24-28/h1-10,15,23,26,28H,11-14,16H2,(H,24,27)/b10-9+

SMILES Code: O=C(NO)/C=C/C1=CC=C(CN(CCO)CCC2=CNC3=C2C=CC=C3)C=C1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Custom

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 379.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Wang H, Cheng F, Woan K, Sahakian E, Merino O, Rock-Klotz J, Vicente-Suarez I, Pinilla-Ibarz J, Wright KL, Seto E, Bhalla K, Villagra A, Sotomayor EM. Histone deacetylase inhibitor LAQ824 augments inflammatory responses in macrophages through transcriptional regulation of IL-10. J Immunol. 2011 Apr 1;186(7):3986-96. doi: 10.4049/jimmunol.1001101. Epub 2011 Mar 2. PubMed PMID: 21368229.

2: Schwarz K, Romanski A, Puccetti E, Wietbrauk S, Vogel A, Keller M, Scott JW, Serve H, Bug G. The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic progenitor cells. Leuk Res. 2011 Jan;35(1):119-25. doi: 10.1016/j.leukres.2010.06.024. Epub 2010 Jul 31. PubMed PMID: 20674020.

3: Cho YS, Whitehead L, Li J, Chen CH, Jiang L, Vögtle M, Francotte E, Richert P, Wagner T, Traebert M, Lu Q, Cao X, Dumotier B, Fejzo J, Rajan S, Wang P, Yan-Neale Y, Shao W, Atadja P, Shultz M. Conformational refinement of hydroxamate-based histone deacetylase inhibitors and exploration of 3-piperidin-3-ylindole analogues of dacinostat (LAQ824). J Med Chem. 2010 Apr 8;53(7):2952-63. doi: 10.1021/jm100007m. PubMed PMID: 20205394.

4: Vo DD, Prins RM, Begley JL, Donahue TR, Morris LF, Bruhn KW, de la Rocha P, Yang MY, Mok S, Garban HJ, Craft N, Economou JS, Marincola FM, Wang E, Ribas A. Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824. Cancer Res. 2009 Nov 15;69(22):8693-9. doi: 10.1158/0008-5472.CAN-09-1456. Epub 2009 Oct 27. PubMed PMID: 19861533; PubMed Central PMCID: PMC2779578.

5: Ellis L, Bots M, Lindemann RK, Bolden JE, Newbold A, Cluse LA, Scott CL, Strasser A, Atadja P, Lowe SW, Johnstone RW. The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy. Blood. 2009 Jul 9;114(2):380-93. doi: 10.1182/blood-2008-10-182758. Epub 2009 Apr 21. PubMed PMID: 19383971.

6: de Bono JS, Kristeleit R, Tolcher A, Fong P, Pacey S, Karavasilis V, Mita M, Shaw H, Workman P, Kaye S, Rowinsky EK, Aherne W, Atadja P, Scott JW, Patnaik A. Phase I pharmacokinetic and pharmacodynamic study of LAQ824, a hydroxamate histone deacetylase inhibitor with a heat shock protein-90 inhibitory profile, in patients with advanced solid tumors. Clin Cancer Res. 2008 Oct 15;14(20):6663-73. doi: 10.1158/1078-0432.CCR-08-0376. PubMed PMID: 18927309.

7: Chung YL, Troy H, Kristeleit R, Aherne W, Jackson LE, Atadja P, Griffiths JR, Judson IR, Workman P, Leach MO, Beloueche-Babari M. Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of a novel histone deacetylase inhibitor, LAQ824, in human colon carcinoma cells and xenografts. Neoplasia. 2008 Apr;10(4):303-13. PubMed PMID: 18392140; PubMed Central PMCID: PMC2288545.

8: Cuneo KC, Fu A, Osusky K, Huamani J, Hallahan DE, Geng L. Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. Anticancer Drugs. 2007 Aug;18(7):793-800. PubMed PMID: 17581301.

9: Kato Y, Salumbides BC, Wang XF, Qian DZ, Williams S, Wei Y, Sanni TB, Atadja P, Pili R. Antitumor effect of the histone deacetylase inhibitor LAQ824 in combination with 13-cis-retinoic acid in human malignant melanoma. Mol Cancer Ther. 2007 Jan;6(1):70-81. PubMed PMID: 17237267.

10: Leyton J, Alao JP, Da Costa M, Stavropoulou AV, Latigo JR, Perumal M, Pillai R, He Q, Atadja P, Lam EW, Workman P, Vigushin DM, Aboagye EO. In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography. Cancer Res. 2006 Aug 1;66(15):7621-9. PubMed PMID: 16885362.



Additional Information

NVP-LAQ824 inhibits histone deacetylase enzymatic activities in vitro and transcriptionally activated the p21 promoter in reporter gene assays. When tested on a variety of solid tumour cell lines, NVP-LAQ824 exhibited selective anti-proliferative effects, inducing cell growth inhibition in some, while inducing cell death in others. To induce cell death, a minimum of 16 h exposure to NVP-LAQ824 is required. Flow cytometry studies revealed that both tumour cell lines and normal diploid fibroblasts arrested in the G2/M phase of the cell cycle after compound treatment. However, an increased sub-G1 population at 48 h (reminiscent of apoptotic cells) was only observed in the cancer cell lines. Annexin V staining data confirmed that NVP-LAQ824 induced apoptosis in tumour cells, but not in normal cells. To relate HDAC inhibition to the anti-proliferative effects of NVP-LAQ824, expression of HDAC 1 was inhibited using antisense and this was sufficient to activate p21 expression, hypophosphorylate Rb and inhibit cell growth. Furthermore, tumour cells treated with NVP-LAQ824 caused acetylation of HSP90 and degradation of its cargo oncoproteins. Finally, NVP-LAQ824 exhibited antitumour effects in a xenograft animal model. To determine if NVP-LAQ824 inhibited histone deacetylases in vivo, tumours treated with the drug were immunoblotted with an antibody specific for acetylated histones H3 and H4 and the results indicated increased histone H3 and 114 acetylation levels in NVP-LAQ824 treated cancer cells. Together, our data indicated that the activity of NVP-LAQ824 was consistent with its intended mechanism of action. This novel HDAC inhibitor is currently in clinical trials as an anticancer agent. see: http://www.ncbi.nlm.nih.gov/pubmed/15171259.