PT  - JOURNAL ARTICLE
AU  - Jing-Xiang Wu
AU  - Dian Ding
AU  - Lei Chen
TI  - The Emerging Structural Pharmacology of ATP-Sensitive Potassium Channels
AID  - 10.1124/molpharm.122.000570
DP  - 2022 Nov 01
TA  - Molecular Pharmacology
PG  - 234--239
VI  - 102
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/102/5/234.short
4100  - http://molpharm.aspetjournals.org/content/102/5/234.full
SO  - Mol Pharmacol2022 Nov 01; 102
AB  - ATP-sensitive potassium channels (KATP) are energy sensors that participate in a range of physiologic processes. These channels are also clinically validated drug targets. For decades, KATP inhibitors have been prescribed for diabetes and KATP activators have been used for the treatment of hypoglycemia, hypertension, and hair loss. In this Emerging Concepts article, we highlight our current knowledge about the drug binding modes observed using cryogenic electron microscopy techniques. The inhibitors and activators bind to two distinct sites in the transmembrane domain of the sulfonylurea receptor (SUR) subunit. We also discuss the possible mechanism of how these drugs allosterically modulate the dimerization of SUR nucleotide-binding domains (NBDs) and thus KATP channel activity.SIGNIFICANCE STATEMENT ATP-sensitive potassium channels (KATP) are fundamental to energy homeostasis, and they participate in many vital physiological processes. KATP channels are important drug targets. Both KATP inhibitors (insulin secretagogues) and KATP activators are broadly used clinically for the treatment of related diseases. Recent cryogenic electron microscopy studies allow us to understand the emerging concept of KATP structural pharmacology.