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 , with an IC value of 3.4 ± 0.2 μM and promising selectivity. ABHD16A has been highlighted as a new target for inflammation-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 toward understanding the significance of hABHD16A inhibition in vivo.
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| http://dx.doi.org/10.1021/acsmedchemlett.8b00442 | DOI Listing |
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Probing the Interactions of Thiazole Abietane Inhibitors with the Human Serine Hydrolases ABHD16A and ABHD12.
ACS Med Chem Lett
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Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
Article Synopsis
- 12-Thiazole abietanes are special compounds that can help stop a brain problem called neuroinflammation by blocking a specific enzyme named hABHD16A.
- Scientists used different techniques to understand which parts of these compounds make them work better against hABHD16A while not affecting another enzyme, hABHD12.
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ACS Med Chem Lett
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Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
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 , with an IC value of 3.4 ± 0.
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