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However, progress in understanding TRPV2 has been limited by a lack of potent and selective pharmacological tools, particularly those targeting the human variant. We aimed to identify and characterise a novel small\u2010molecule activator of TRPV2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We screened a compound library using Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imaging in HEK293 cells stably expressing mouse TRPV2. The lead compound AV2\u20101 was validated by concentration\u2013response analyses, microfluorometric Ca\n                      <jats:sup>2+<\/jats:sup>\n                      assays, and electrophysiological recordings. Structural insights were obtained from cryoEM of TRPV2 in complex with AV2\u20101, and mutagenesis was performed to confirm binding site residues. The efficacy of AV2\u20101 was assessed in human peripheral blood\u2010derived macrophages by Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imaging, whole\u2010cell electrophysiology and TIRF microscopy to detect Ca\n                      <jats:sup>2+<\/jats:sup>\n                      microdomains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      AV2\u20101 is a novel TRPV2 activator showing robust efficacy across mouse, rat and human orthologues. Structural analysis reveals that AV2\u20101 stabilises the channel in its active conformation by binding to an established intracellular pocket via TRPV2\u2010specific residues His165 and Cys157, as confirmed by mutagenesis experiments. AV2\u20101 induces TRPV2\u2010dependent global [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      signals, ionic currents and localised subplasmalemmal Ca\n                      <jats:sup>2+<\/jats:sup>\n                      microdomains in human peripheral blood\u2010derived macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      AV2\u20101 represents a novel pharmacological tool for probing TRPV2 function in immune cells, combining improved selectivity and potency with low toxicity. Its ability to activate human TRPV2 and elicit physiologically relevant Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signals highlights its potential for advancing TRPV2 research and for therapeutic exploration in immune modulation and disease contexts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70413","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:52:55Z","timestamp":1774932775000},"page":"3538-3557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Defining AV2\u20101 as a novel pharmacological probe to target human and rodent TRPV2"],"prefix":"10.1111","volume":"183","author":[{"given":"Andrea","family":"Leipe","sequence":"first","affiliation":[{"name":"Rudolf\u2010Boehm\u2010Institute of Pharmacology and Toxicology, Leipzig University, Faculty of Medicine  Leipzig 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