Largazole

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 598400

CAS#: 1009815-87-5

Description: Largazole is a potent and selective histone deacetylase (HDAC) inhibitor. It is also an antiproliferative agent from Symploca.


Chemical Structure

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Largazole
CAS# 1009815-87-5

Theoretical Analysis

MedKoo Cat#: 598400
Name: Largazole
CAS#: 1009815-87-5
Chemical Formula: C29H42N4O5S3
Exact Mass: 622.2317
Molecular Weight: 622.85
Elemental Analysis: C, 55.92; H, 6.80; N, 9.00; O, 12.84; S, 15.44

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

Request quote for custom synthesis

Synonym: Largazole;

IUPAC/Chemical Name: S-((E)-4-((12Z,22Z,24R,5S,8S)-5-isopropyl-24-methyl-3,6,10-trioxo-24,25-dihydro-7-oxa-4,11-diaza-1(4,2),2(2,4)-dithiazolacyclododecaphane-8-yl)but-3-en-1-yl) octanethioate

InChi Key: AXESYCSCGBQJBL-SZPBEECKSA-N

InChi Code: InChI=1S/C29H42N4O5S3/c1-5-6-7-8-9-13-24(35)39-14-11-10-12-20-15-22(34)30-16-23-31-21(17-40-23)26-33-29(4,18-41-26)28(37)32-25(19(2)3)27(36)38-20/h10,12,17,19-20,25H,5-9,11,13-16,18H2,1-4H3,(H,30,34)(H,32,37)/b12-10+/t20-,25+,29+/m1/s1

SMILES Code: O=C([C@H](C(C)C)NC([C@@]1(C)N=C(SC1)c2csc(CN3)n2)=O)O[C@H](/C=C/CCSC(CCCCCCC)=O)CC3=O

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 Customs.

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

Shelf Life: >3 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 622.85 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: Yu M, Salvador LA, Sy SK, Tang Y, Singh RS, Chen QY, Liu Y, Hong J, Derendorf H, Luesch H. Largazole pharmacokinetics in rats by LC-MS/MS. Mar Drugs. 2014 Mar 20;12(3):1623-40. doi: 10.3390/md12031623. PubMed PMID: 24658499; PubMed Central PMCID: PMC3967229.

2: Decroos C, Clausen DJ, Haines BE, Wiest O, Williams RM, Christianson DW. Variable active site loop conformations accommodate the binding of macrocyclic largazole analogues to HDAC8. Biochemistry. 2015 Mar 31;54(12):2126-35. doi: 10.1021/acs.biochem.5b00010. Epub 2015 Mar 20. PubMed PMID: 25793284; PubMed Central PMCID: PMC4382410.

3: Pilon JL, Clausen DJ, Hansen RJ, Lunghofer PJ, Charles B, Rose BJ, Thamm DH, Gustafson DL, Bradner JE, Williams RM. Comparative pharmacokinetic properties and antitumor activity of the marine HDACi Largazole and Largazole peptide isostere. Cancer Chemother Pharmacol. 2015 Apr;75(4):671-82. doi: 10.1007/s00280-015-2675-1. Epub 2015 Jan 24. PubMed PMID: 25616967; PubMed Central PMCID: PMC4368451.

4: Zhou H, Jiang S, Chen J, Ren X, Jin J, Su SB. Largazole, an inhibitor of class I histone deacetylases, attenuates inflammatory corneal neovascularization. Eur J Pharmacol. 2014 Oct 5;740:619-26. doi: 10.1016/j.ejphar.2014.06.019. Epub 2014 Jun 26. PubMed PMID: 24973692.

5: Almaliti J, Al-Hamashi AA, Negmeldin AT, Hanigan CL, Perera L, Pflum MK, Casero RA Jr, Tillekeratne LM. Largazole Analogues Embodying Radical Changes in the Depsipeptide Ring: Development of a More Selective and Highly Potent Analogue. J Med Chem. 2016 Dec 8;59(23):10642-10660. Epub 2016 Nov 21. PubMed PMID: 27809521; PubMed Central PMCID: PMC5574184.

6: Bhansali P, Hanigan CL, Perera L, Casero RA Jr, Tillekeratne LM. Synthesis and biological evaluation of largazole analogues with modified surface recognition cap groups. Eur J Med Chem. 2014 Oct 30;86:528-41. doi: 10.1016/j.ejmech.2014.09.009. Epub 2014 Sep 6. PubMed PMID: 25203782; PubMed Central PMCID: PMC4188730.

7: Kim B, Park H, Salvador LA, Serrano PE, Kwan JC, Zeller SL, Chen QY, Ryu S, Liu Y, Byeon S, Luesch H, Hong J. Evaluation of class I HDAC isoform selectivity of largazole analogues. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3728-31. doi: 10.1016/j.bmcl.2014.07.006. Epub 2014 Jul 9. PubMed PMID: 25070421; PubMed Central PMCID: PMC4135083.

8: Salvador LA, Park H, Al-Awadhi FH, Liu Y, Kim B, Zeller SL, Chen QY, Hong J, Luesch H. Modulation of Activity Profiles for Largazole-Based HDAC Inhibitors through Alteration of Prodrug Properties. ACS Med Chem Lett. 2014 Jul 7;5(8):905-10. doi: 10.1021/ml500170r. eCollection 2014 Aug 14. PubMed PMID: 25147612; PubMed Central PMCID: PMC4137384.

9: Liu Y, Wang Z, Wang J, Lam W, Kwong S, Li F, Friedman SL, Zhou S, Ren Q, Xu Z, Wang X, Ji L, Tang S, Zhang H, Lui EL, Ye T. A histone deacetylase inhibitor, largazole, decreases liver fibrosis and angiogenesis by inhibiting transforming growth factor-β and vascular endothelial growth factor signalling. Liver Int. 2013 Apr;33(4):504-15. doi: 10.1111/liv.12034. Epub 2012 Dec 26. PubMed PMID: 23279742.

10: Hong J, Luesch H. Largazole: from discovery to broad-spectrum therapy. Nat Prod Rep. 2012 Apr;29(4):449-56. doi: 10.1039/c2np00066k. Epub 2012 Feb 14. Review. PubMed PMID: 22334030; PubMed Central PMCID: PMC4777309.

11: Wu LC, Wen ZS, Qiu YT, Chen XQ, Chen HB, Wei MM, Liu Z, Jiang S, Zhou GB. Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells. ACS Med Chem Lett. 2013 Aug 12;4(10):921-6. doi: 10.1021/ml400093y. eCollection 2013 Oct 10. PubMed PMID: 24900585; PubMed Central PMCID: PMC4027503.

12: Clausen DJ, Smith WB, Haines BE, Wiest O, Bradner JE, Williams RM. Modular synthesis and biological activity of pyridyl-based analogs of the potent Class I Histone Deacetylase Inhibitor Largazole. Bioorg Med Chem. 2015 Aug 1;23(15):5061-74. doi: 10.1016/j.bmc.2015.03.063. Epub 2015 Mar 31. PubMed PMID: 26054247; PubMed Central PMCID: PMC4626217.

13: Ungermannova D, Parker SJ, Nasveschuk CG, Wang W, Quade B, Zhang G, Kuchta RD, Phillips AJ, Liu X. Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (e1). PLoS One. 2012;7(1):e29208. doi: 10.1371/journal.pone.0029208. Epub 2012 Jan 18. PubMed PMID: 22279528; PubMed Central PMCID: PMC3261141.

14: Guerra-Bubb JM, Bowers AA, Smith WB, Paranal R, Estiu G, Wiest O, Bradner JE, Williams RM. Synthesis and HDAC inhibitory activity of isosteric thiazoline-oxazole largazole analogs. Bioorg Med Chem Lett. 2013 Nov 1;23(21):6025-8. doi: 10.1016/j.bmcl.2013.06.012. Epub 2013 Jun 18. PubMed PMID: 24035339; PubMed Central PMCID: PMC3859309.

15: Cole KE, Dowling DP, Boone MA, Phillips AJ, Christianson DW. Structural basis of the antiproliferative activity of largazole, a depsipeptide inhibitor of the histone deacetylases. J Am Chem Soc. 2011 Aug 17;133(32):12474-7. doi: 10.1021/ja205972n. Epub 2011 Jul 26. PubMed PMID: 21790156; PubMed Central PMCID: PMC3162211.

16: Reddy DN, Ballante F, Chuang T, Pirolli A, Marrocco B, Marshall GR. Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors. J Med Chem. 2016 Feb 25;59(4):1613-33. doi: 10.1021/acs.jmedchem.5b01632. Epub 2016 Jan 7. PubMed PMID: 26681404.

17: Ahmed S, Riegsecker S, Beamer M, Rahman A, Bellini JV, Bhansali P, Tillekeratne LM. Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts. Toxicol Appl Pharmacol. 2013 Jul 15;270(2):87-96. doi: 10.1016/j.taap.2013.04.014. Epub 2013 Apr 28. PubMed PMID: 23632129; PubMed Central PMCID: PMC3766723.

18: Bhansali P, Hanigan CL, Casero RA, Tillekeratne LM. Largazole and analogues with modified metal-binding motifs targeting histone deacetylases: synthesis and biological evaluation. J Med Chem. 2011 Nov 10;54(21):7453-63. doi: 10.1021/jm200432a. Epub 2011 Oct 10. PubMed PMID: 21936551; PubMed Central PMCID: PMC3208063.

19: Lee SU, Kwak HB, Pi SH, You HK, Byeon SR, Ying Y, Luesch H, Hong J, Kim SH. In Vitro and In Vivo Osteogenic Activity of Largazole. ACS Med Chem Lett. 2011 Mar 10;2(3):248-251. PubMed PMID: 21666868; PubMed Central PMCID: PMC3109915.

20: Liu Y, Salvador LA, Byeon S, Ying Y, Kwan JC, Law BK, Hong J, Luesch H. Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor. J Pharmacol Exp Ther. 2010 Nov;335(2):351-61. doi: 10.1124/jpet.110.172387. Epub 2010 Aug 25. PubMed PMID: 20739454; PubMed Central PMCID: PMC2967399.