Ahonen Tiina J, Savinainen Juha R, Yli-Kauhaluoma Jari, Kalso Eija, Laitinen Jarmo T, Moreira Vânia M
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
School of Medicine, Institute of Biomedicine, University of Eastern Finland, 80101 Kuopio, Finland.
ACS Med Chem Lett. 2018 Nov 13;9(12):1269-1273. doi: 10.1021/acsmedchemlett.8b00442. eCollection 2018 Dec 13.
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.
对一个内部化合物文库进行筛选后，确定12-噻唑枞酸类化合物是人类代谢型丝氨酸水解酶的一类新型可逆抑制剂。对首个活性命中化合物的进一步优化得到了2-甲基噻唑衍生物，其IC值为3.4±0.2μM，且具有良好的选择性。ABHD16A已被视为炎症介导性疼痛的一个新靶点，尽管尚未有关于hABHD16A（人类ABHD16A）选择性抑制剂的报道。我们的研究表明枞酸型二萜类化合物是设计选择性ABHD16A抑制剂的一个有吸引力的起点，这将有助于理解体内抑制hABHD16A的意义。
