Journal of medicinal chemistry · 2026
First Structure-Activity-Relationship Study of Potent G2A Antagonists.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hernandez-Olmos Victor, Heering Jan, Lillich Felix F, Marinescu Beatrice, Nevermann Sheila, Ehrler Johanna H M, Radchenko Dmytro S, Moroz Yurii S, Kaiser Astrid, Krämer Andreas, Knapp Stefan, Schubert-Zsilavecz Manfred, Alnouri Mohamad Wessam, Offermanns Stefan, Steinhilber Dieter, Sisignano Marco, Proschak Ewgenij
Аннотация
G2A inhibition has recently been proposed as a novel therapeutic approach to treat oxaliplatin-induced neuropathic pain (OINP) and breast cancer. However, very few G2A antagonists are known to date. In this study, we report the discovery of a novel series of G2A antagonists developed within our research group, along with the first comprehensive structure-activity relationship (SAR) investigation for this class of compounds. Utilizing a rational design approach, we systematically explored the effects of structural modifications on G2A receptor binding and functional activity. The SAR study identified key molecular features critical for potent G2A inhibition. Two of the newly discovered compounds exhibited submicromolar activity and acceptable selectivity profile among GPCRs.