Thailanstatin A

  • CAT Number: I037191
  • CAS Number: 1426953-21-0
  • Molecular Formula: C28H41NO9
  • Molecular Weight: 535.63
  • Purity: 98%
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Thailanstatin A(Cat No.:I037191) is a natural product isolated from a marine-derived Streptomyces sp. that exhibits potent antiproliferative activity against a variety of cancer cell lines. It acts as a potent inhibitor of the proteasome-associated deubiquitinase USP9X, which is involved in regulating the degradation of several important cellular proteins. Thailanstatin A has been shown to induce apoptosis and inhibit tumor growth in vivo and may have potential as a therapeutic agent for the treatment of cancer.

Catalog Number I037191
CAS Number 1426953-21-0
Molecular Formula

C28H41NO9

Purity 98
Solubility Soluble in DMSO
Storage Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
IUPAC Name 2-[(3R,4R,5R,7S)-5-[(1E,3E)-5-[(2S,3S,5R,6R)-5-[[(Z,4S)-4-acetyloxypent-2-enoyl]amino]-3,6-dimethyloxan-2-yl]-3-methylpenta-1,3-dienyl]-4-hydroxy-1,6-dioxaspiro[2.5]octan-7-yl]acetic acid
InChI InChI=1S/C28H41NO9/c1-16(7-10-24-27(34)28(15-35-28)14-21(38-24)13-26(32)33)6-9-23-17(2)12-22(19(4)37-23)29-25(31)11-8-18(3)36-20(5)30/h6-8,10-11,17-19,21-24,27,34H,9,12-15H2,1-5H3,(H,29,31)(H,32,33)/b10-7+,11-8-,16-6+/t17-,18-,19+,21+,22+,23-,24+,27+,28+/m0/s1
InChIKey GJKQDOMCDFJANR-FUDLAKRJSA-N
SMILES O=C(O)C[C@H](C1)O[C@H](/C=C/C(C)=C/C[C@@H]2O[C@H](C)[C@H](NC(/C=C[C@@H](OC(C)=O)C)=O)C[C@@H]2C)[C@@H](O)[C@@]31CO3
Reference

1: Nicolaou KC, Rhoades D, Kumar SM. Total Syntheses of Thailanstatins A-C, Spliceostatin D, and Analogues Thereof. Stereodivergent Synthesis of Tetrasubstituted Dihydro- and Tetrahydropyrans and Design, Synthesis, Biological Evaluation, and Discovery of Potent Antitumor Agents. J Am Chem Soc. 2018 Jul 5;140(26):8303-8320. doi: 10.1021/jacs.8b04634. Epub 2018 Jun 26. PMID: 29943984.
2: Ghosh AK, Veitschegger AM, Nie S, Relitti N, MacRae AJ, Jurica MS. Enantioselective Synthesis of Thailanstatin A Methyl Ester and Evaluation of in Vitro Splicing Inhibition. J Org Chem. 2018 May 4;83(9):5187-5198. doi: 10.1021/acs.joc.8b00593. Epub 2018 Apr 26. PMID: 29696980; PMCID: PMC5972027.
3: Wang B, Lo UG, Wu K, Kapur P, Liu X, Huang J, Chen W, Hernandez E, Santoyo J, Ma SH, Pong RC, He D, Cheng YQ, Hsieh JT. Developing new targeting strategy for androgen receptor variants in castration resistant prostate cancer. Int J Cancer. 2017 Nov 15;141(10):2121-2130. doi: 10.1002/ijc.30893. Epub 2017 Jul 31. PMID: 28722220; PMCID: PMC5777133.
4: Kulkarni C, Finley JE, Bessire AJ, Zhong X, Musto S, Graziani EI. Development of Fluorophore-Labeled Thailanstatin Antibody-Drug Conjugates for Cellular Trafficking Studies. Bioconjug Chem. 2017 Apr 19;28(4):1041-1047. doi: 10.1021/acs.bioconjchem.6b00718. Epub 2017 Mar 1. PMID: 28191936.
5: Puthenveetil S, Loganzo F, He H, Dirico K, Green M, Teske J, Musto S, Clark T, Rago B, Koehn F, Veneziale R, Falahaptisheh H, Han X, Barletta F, Lucas J, Subramanyam C, O’Donnell CJ, Tumey LN, Sapra P, Gerber HP, Ma D, Graziani EI. Natural Product Splicing Inhibitors: A New Class of Antibody-Drug Conjugate (ADC) Payloads. Bioconjug Chem. 2016 Aug 17;27(8):1880-8. doi: 10.1021/acs.bioconjchem.6b00291. Epub 2016 Jul 28. PMID: 27412791.
6: Nicolaou KC, Rhoades D, Lamani M, Pattanayak MR, Kumar SM. Total Synthesis of Thailanstatin A. J Am Chem Soc. 2016 Jun 22;138(24):7532-5. doi: 10.1021/jacs.6b04781. Epub 2016 Jun 13. PMID: 27266914.
7: Liu X, Zhu H, Biswas S, Cheng YQ. Improved production of cytotoxic thailanstatins A and D through metabolic engineering of Burkholderia thailandensis MSMB43 and pilot scale fermentation. Synth Syst Biotechnol. 2016 Apr 1;1(1):34-38. doi: 10.1016/j.synbio.2016.02.002. PMID: 29062925; PMCID: PMC5640593.
8: Eustáquio AS, Chang LP, Steele GL, O Donnell CJ, Koehn FE. Biosynthetic engineering and fermentation media development leads to gram-scale production of spliceostatin natural products in Burkholderia sp. Metab Eng. 2016 Jan;33:67-75. doi: 10.1016/j.ymben.2015.11.003. Epub 2015 Nov 24. PMID: 26620532.
9: Jain A, Liu X, Wordinger RJ, Yorio T, Cheng YQ, Clark AF. Effects of thailanstatins on glucocorticoid response in trabecular meshwork and steroid- induced glaucoma. Invest Ophthalmol Vis Sci. 2013 May 3;54(5):3137-42. doi: 10.1167/iovs.12-11480. PMID: 23548621; PMCID: PMC3645369.
10: Liu X, Biswas S, Berg MG, Antapli CM, Xie F, Wang Q, Tang MC, Tang GL, Zhang L, Dreyfuss G, Cheng YQ. Genomics-guided discovery of thailanstatins A, B, and C As pre-mRNA splicing inhibitors and antiproliferative agents from Burkholderia thailandensis MSMB43. J Nat Prod. 2013 Apr 26;76(4):685-93. doi: 10.1021/np300913h. Epub 2013 Mar 21. PMID: 23517093; PMCID: PMC3696399.

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