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ECNU and Zhejiang University have jointly discovered a new activation mechanism for small molecules to directly open the KCNQ2 channel, offering a new path for drug discovery of agonists.
Drugs are generally divided into inhibitors and agonists; the former can reduce the activity of targets while the latter can increase the activity of targets. Ion channels have a very wide range of physiological functions and are one of the top three drug targets, whose inhibitors and agonists are important directions for drug development. At present, drugs targeting ion channels are mainly inhibitors, also known as blockers, whose mechanism of action is clear, that is, blocking the entry and exit pathways of ions. However, the discovery of agonists for targeted ion channels encounters challenges, and there is an urgent need to establish agonist regulation theories to promote the rational development of agonist drugs.
Ion channels are an important source of drug targets and potential drug targets for they have a wide range of significant physiological and pathological functions. However, it is relatively difficult to discover small molecule modulators of ion channels, which has become a bottleneck in the development of drugs for targeted ion channels.
Yang Huaiyu’s research team from the School of Life Sciences of ECNU has been engaged in developing new regulation theories for ion channels, and has proposed non-classical regulation mechanisms such as “targeting intermediate states” and “ligand-to-ion modulation”, laying the foundation for the design of drugs for ion channels. Recently, the team has collaborated with Guo Jiangtao’s research team from the School of Basic Medical Sciences of Zhejiang University to reveal a new regulatory mechanism for small molecules to directly open the channel. The research results were published online in Nature Chemical Biology titled “A small-molecule activation mechanism that directly opens the KCNQ2 channel” on January 2nd, 2024.
The first authors of the paper include Zhang Shaoying, a graduate student of ECNU, Ma Demin, a graduate student of Zhejiang University, and Wang Kun and Li Ya, graduate students of ECNU. The corresponding authors include Prof. Yang Huaiyu from ECNU, Youth Researcher Zhang Qiansen of ECNU, and Researcher Guo Jiangtao of Zhejiang University. This research was funded by the Strategic Science and Technology Innovation Cooperation Key Fund of the National Key R&D Program of China and other funds.
Source: School of Life Sciences