Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A

Tiina J. Ahonen, Juha R. Savinainen, Jari Yli-Kauhaluoma, Eija Kalso, Jarmo T. Laitinen, Vânia M. Moreira

Research output: Contribution to journalArticle

2 Citations (Scopus)
2 Downloads (Pure)

Abstract

Screening of an in-house library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative 18, with an IC50 value of 3.4 ± 0.2 µM and promising selectivity. ABHD16A has been highlighted as a new target for in-flammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. Our study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute towards understanding the significance of hABHD16A inhibition in vivo.
Original languageEnglish
Pages (from-to)1269-1273
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume9
Issue number12
Early online date13 Nov 2018
DOIs
Publication statusPublished - 13 Nov 2018

Keywords

  • dehydroabietic acid
  • hABHD16A inhibitor
  • lysophosphatidylserine
  • metabolic serine hydrolase

Fingerprint Dive into the research topics of 'Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A'. Together they form a unique fingerprint.

  • Cite this