2. Academic Validation
  3. Selectivity of microbial acyl-CoA: cholesterol acyltransferase inhibitors toward isozymes

Selectivity of microbial acyl-CoA: cholesterol acyltransferase inhibitors toward isozymes

  • J Antibiot (Tokyo). 2007 Jan;60(1):43-51. doi: 10.1038/ja.2007.6.
Taichi Ohshiro 1,  Lawrence L Rudel,  Satoshi Omura,  Hiroshi Tomoda
Affiliations

Affiliation

  • 1 Kitasato Institute for Life Sciences, Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
PMID: 17390588 DOI: 10.1038/ja.2007.6
Abstract

The selectivity of microbial inhibitors of acyl-CoA: cholesterol Acyltransferase (ACAT) toward the two isozymes, ACAT1 and ACAT2, was assessed in cell-based assays. Purpactin A (IC50 values of ACAT1 vs. IC50 values of ACAT2; 2.5 microM vs. 1.5 microM), terpendole C (10 microM vs. 10 microM), glisoprenin A (4.3 microM vs. 10 microM), spylidone (25 microM vs. 5.0 microM) and synthetic CL-283,546 (0.1 microM vs. 0.09 microM) inhibited ACAT1 and ACAT2 to similar extents. Beauveriolides I (0.6 microM vs. 20 microM) and III (0.9 microM vs. >20 microM) inhibited ACAT1 rather selectively, while pyripyropenes A (>80 microM vs. 0.07 microM), B (48 microM vs. 2.0 microM), C (32 microM vs. 0.36 microM) and D (38 microM vs. 1.5 microM) showed selective inhibition against ACAT2. In particular, pyripyropene A was found to be the most selective ACAT2 Inhibitor with a selective index of more than 1,000.

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