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530196 Pladienolide B, Streptomyces sp. - CAS 445493-23-2 - Calbiochem

A cell-permeable inhibitor of mRNA splicing that directly target the splicesome-associated protein 130 and impair U2 small nuclear ribonucleoprotein (U2 snRNP) interaction with pre-mRNA.

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Sinónimos: (2S,3S,6S,7R,10R,E)-7,10-dihydroxy-2-((S,2E,4E)-7-((2R,3R)-3-((2R,3S)-3-hydroxypentan-2-yl), Pla-B

Primary Target: SAP130, splicing factor SF3b subunit 3
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      Descripción

      Tabla espec. clave

      CAS #Empirical Formula
      445493-23-2C₃₀H₄₈O₈
      Description
      OverviewA cell-permeable, antitumor macrolide that acts as a time- and dose-dependent inhibitor of mRNA splicing. Shown to directly target the splicesome-associated protein 130 (SAP130, splicing factor SF3b subunit 3) and impair U2 small nuclear ribonucleoprotein (U2 snRNP) interaction with pre-mRNA causing unspliced or incompletely spliced pre-mRNA accumulation and altered gene expression. Exhibits potent anti-proliferative effect on WiDr and DLD1 colon cancer cell lines (IC50 = 500 pM and 8.5 nM, respectively) and is reported to down-regulate hypoxia-induced VEGF gene expression (IC50 = 1.8 nM in U251 cells). Blocks cell cycle by arresting progression at both G1 and G2/M phases. However, it does not affect the proliferation of resistant type of WiDr and DLD1 cells bearing R1074H mutation in SF3B1 gene. Inhibits tumor growth in WiDr tumor bearing nude mice and in a BSY-1 xenograft murine model (~5 – 10 mg/kg/day).
      Catalogue Number530196
      Brand Family Calbiochem®
      Synonyms(2S,3S,6S,7R,10R,E)-7,10-dihydroxy-2-((S,2E,4E)-7-((2R,3R)-3-((2R,3S)-3-hydroxypentan-2-yl), Pla-B
      References
      ReferencesYokoi, A., et al. 2011. FEBS J. 278, 4870.
      O'Brien, K., et al. 2008. J. Biol. Chem. 283, 33147.
      Kotake, Y., et al. 2007. Nat. Chem. Biol. 9, 570.
      Mizui, T., et al. 2004. J. Antibiot. 57, 188.
      Sakai, T., et al. 2004. J. Antibiot. 57, 180.
      Sakai, T., et al. 2004. J. Antibiot. 57, 173.
      Product Information
      CAS number445493-23-2
      FormWhite solid
      Hill FormulaC₃₀H₄₈O₈
      Chemical formulaC₃₀H₄₈O₈
      Quality LevelMQ100
      Biological Information
      Primary TargetSAP130, splicing factor SF3b subunit 3
      Purity≥95% by HPLC
      Physicochemical Information
      Cell permeableY
      Storage and Shipping Information
      Ship Code Ambient Temperature Only
      Toxicity Standard Handling
      Storage -20°C
      Protect from Light Protect from light
      Do not freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
      Packaging Information
      Packaged under inert gas Packaged under inert gas
      Global Trade Item Number
      Número de referencia GTIN
      530196 0