Spliceostatin A

  • CAT Number: I009788
  • CAS Number: 391611-36-2
  • Molecular Formula: C28H43NO8
  • Molecular Weight: 521.651
  • Purity: ≥95%
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Spliceostatin A (CAT: I009788) is a natural product derived from the bacterium Pseudomonas chartarum. It is a potent inhibitor of pre-mRNA splicing, a crucial step in gene expression. Spliceostatin A targets the spliceosome, a large ribonucleoprotein complex responsible for the removal of introns and the splicing together of exons during mRNA maturation. By inhibiting the spliceosome, spliceostatin A disrupts the splicing process and alters mRNA processing, leading to the accumulation of aberrant splicing products and ultimately affecting protein production. Due to its ability to modulate splicing, spliceostatin A has attracted interest in both basic research and potential therapeutic applications for diseases related to splicing dysregulation, such as cancer.


Catalog Number I009788
CAS Number 391611-36-2
Synonyms

Spliceostatin A; (2Z,4S)-4-(Acetyloxy)-N-[(2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-methoxy-7-methyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-2-pentenamide

Molecular Formula C28H43NO8
Purity ≥95%
Storage Room temperature
IUPAC Name [(Z,2S)-5-[[(2R,3R,5S,6S)-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-methoxy-7-methyl-1,6-dioxaspiro[2.5]octan-5-yl]-3-methylpenta-2,4-dienyl]-2,5-dimethyloxan-3-yl]amino]-5-oxopent-3-en-2-yl] acetate
InChI InChI=1S/C28H43NO8/c1-17(9-12-24-26(32)28(16-34-28)15-27(6,33-7)37-24)8-11-23-18(2)14-22(20(4)36-23)29-25(31)13-10-19(3)35-21(5)30/h8-10,12-13,18-20,22-24,26,32H,11,14-16H2,1-7H3,(H,29,31)/b12-9+,13-10-,17-8+/t18-,19-,20+,22+,23-,24+,26+,27-,28+/m0/s1
InChIKey XKSGIJNRMWHQIQ-CGPJBNNXSA-N
SMILES CC1CC(C(OC1CC=C(C)C=CC2C(C3(CC(O2)(C)OC)CO3)O)C)NC(=O)C=CC(C)OC(=O)C
Reference

1: Yoshimoto R, Kaida D, Furuno M, Burroughs AM, Noma S, Suzuki H, Kawamura Y,
Hayashizaki Y, Mayeda A, Yoshida M. Global analysis of pre-mRNA subcellular
localization following splicing inhibition by spliceostatin A. RNA. 2017
Jan;23(1):47-57. Epub 2016 Oct 17. PubMed PMID: 27754875; PubMed Central PMCID:
PMC5159648.

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2: Larrayoz M, Blakemore SJ, Dobson RC, Blunt MD, Rose-Zerilli MJ, Walewska R,
Duncombe A, Oscier D, Koide K, Forconi F, Packham G, Yoshida M, Cragg MS,
Strefford JC, Steele AJ. The SF3B1 inhibitor spliceostatin A (SSA) elicits
apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1.
Leukemia. 2016 Feb;30(2):351-60. doi: 10.1038/leu.2015.286. Epub 2015 Oct 21.
PubMed PMID: 26488112.

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3: Ghosh AK, Chen ZH, Effenberger KA, Jurica MS. Enantioselective total syntheses
of FR901464 and spliceostatin A and evaluation of splicing activity of key
derivatives. J Org Chem. 2014 Jun 20;79(12):5697-709. doi: 10.1021/jo500800k.
Epub 2014 May 30. PubMed PMID: 24873648; PubMed Central PMCID: PMC4066912.
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4: Ghosh AK, Chen ZH. Enantioselective syntheses of FR901464 and spliceostatin A:
potent inhibitors of spliceosome. Org Lett. 2013 Oct 4;15(19):5088-91. doi:
10.1021/ol4024634. Epub 2013 Sep 19. PubMed PMID: 24050251; PubMed Central PMCID:
PMC3827971.
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5: Corrionero A, Mi&#241;ana B, Valcárcel J. Reduced fidelity of branch point
recognition and alternative splicing induced by the anti-tumor drug spliceostatin
A. Genes Dev. 2011 Mar 1;25(5):445-59. doi: 10.1101/gad.2014311. PubMed PMID:
21363963; PubMed Central PMCID: PMC3049286.

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6: Furumai R, Uchida K, Komi Y, Yoneyama M, Ishigami K, Watanabe H, Kojima S,
Yoshida M. Spliceostatin A blocks angiogenesis by inhibiting global gene
expression including VEGF. Cancer Sci. 2010 Nov;101(11):2483-9. doi:
10.1111/j.1349-7006.2010.01686.x. PubMed PMID: 20726856.

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7: Roybal GA, Jurica MS. Spliceostatin A inhibits spliceosome assembly subsequent
to prespliceosome formation. Nucleic Acids Res. 2010 Oct;38(19):6664-72. doi:
10.1093/nar/gkq494. Epub 2010 Jun 6. PubMed PMID: 20529876; PubMed Central PMCID:
PMC2965229.
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8: Lo CW, Kaida D, Nishimura S, Matsuyama A, Yashiroda Y, Taoka H, Ishigami K,
Watanabe H, Nakajima H, Tani T, Horinouchi S, Yoshida M. Inhibition of splicing
and nuclear retention of pre-mRNA by spliceostatin A in fission yeast. Biochem
Biophys Res Commun. 2007 Dec 21;364(3):573-7. Epub 2007 Oct 15. PubMed PMID:
17961508.
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9: Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, Ishigami K, Watanabe H,
Kitahara T, Yoshida T, Nakajima H, Tani T, Horinouchi S, Yoshida M. Spliceostatin
A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat
Chem Biol. 2007 Sep;3(9):576-83. Epub 2007 Jul 22. PubMed PMID: 17643111.

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