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Premature termination of the anagen phase accelerates the transition of hair follicles into the catagen and telogen phases, leading to hair loss. Inhibiting the mitochondrial pyruvate carrier (MPC), which prevents pyruvate from entering mitochondria, enhances lactate synthesis. This activates HFSCs and initiates a new hair growth cycle. To develop safer and more effective MPC inhibitors, we designed and synthesized a series of 2\u2010phenyl\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyrrole derivatives based on UK5099 and JXL066 by scaffold hopping and structural optimization strategies. In\u00a0vitro lactate release assay identified 14 compounds that exhibited superior biological activity compared to UK5099, with\n                    <jats:bold>5a<\/jats:bold>\n                    being the most potent compound. The ADMET predictions suggested that\n                    <jats:bold>5a<\/jats:bold>\n                    possesses low toxicity and moderate skin permeability, supporting its suitability for topical dermal formulations. Further evaluation demonstrated\n                    <jats:bold>5a<\/jats:bold>\n                    had good stability in topical formulation and low skin irritation in repeated acute irritation tests. Hair regrowth experiments in C57BL\/6J mice showed that\n                    <jats:bold>5a<\/jats:bold>\n                    significantly promoted hair regrowth and accelerated the transition from telogen to anagen, accompanied by increased hair follicle density. These findings validate MPC as a promising target and highlight\n                    <jats:bold>5a<\/jats:bold>\n                    as a potential therapeutic agent for the treatment of hair loss.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70306","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:12:19Z","timestamp":1782213139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel 2\u2010Phenyl\u20101\n                    <i>H<\/i>\n                    \u2010Pyrrole Derivatives as Mitochondrial Pyruvate Carrier Inhibitors to Treat Hair Loss"],"prefix":"10.1111","volume":"107","author":[{"given":"Xingyu","family":"Wu","sequence":"first","affiliation":[{"name":"Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. 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