2. Academic Validation
  3. Selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3 that impairs cancer cell survival

Selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3 that impairs cancer cell survival

  • ACS Chem Biol. 2015 Apr 17;10(4):925-32. doi: 10.1021/cb500893q.
Jae Won Chang,  Andrea M Zuhl,  Anna E Speers,  Sherry Niessen,  Steven J Brown,  Melinda M Mulvihill 1,  Yi Chiao Fan 2,  Timothy P Spicer,  Mark Southern,  Louis Scampavia,  Virneliz Fernandez-Vega,  Melissa M Dix,  Michael D Cameron,  Peter S Hodder,  Hugh Rosen,  Daniel K Nomura 1,  Ohyun Kwon 2,  Ku-Lung Hsu,  Benjamin F Cravatt
Affiliations

Affiliations

  • 1 ⊥Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, California 94720, United States.
  • 2 #Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States.
PMID: 25602368 DOI: 10.1021/cb500893q
Abstract

Platelet-activating factor acetylhydrolases (PAFAHs) 1b2 and 1b3 are poorly characterized serine hydrolases that form a complex with a noncatalytic protein (1b1) to regulate brain development, spermatogenesis, and Cancer pathogenesis. Determining physiological substrates and biochemical functions for the PAFAH1b complex would benefit from selective chemical probes that can perturb its activity in living systems. Here, we report a class of tetrahydropyridine reversible inhibitors of PAFAH1b2/3 discovered using a fluorescence polarization-activity-based protein profiling (fluopol-ABPP) screen of the NIH 300,000+ compound library. The most potent of these agents, P11, exhibited IC50 values of ∼40 and 900 nM for PAFAH1b2 and 1b3, respectively. We confirm selective inhibition of PAFAH1b2/3 in Cancer cells by P11 using an ABPP protocol adapted for in situ analysis of reversible inhibitors and show that this compound impairs tumor cell survival, supporting a role for PAFAH1b2/3 in Cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-111053
    ≥98.0%, PAFAH1b2/1b3抑制剂
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