{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:30:56Z","timestamp":1788345056704,"version":"build-2803163510"},"reference-count":24,"publisher":"American Chemical Society (ACS)","issue":"20","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010023","name":"Natural Science Research of Jiangsu Higher Education Institutions of China","doi-asserted-by":"publisher","award":["21KJB350012"],"award-info":[{"award-number":["21KJB350012"]}],"id":[{"id":"10.13039\/501100010023","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2700200"],"award-info":[{"award-number":["2021YFC2700200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007166","name":"Jiangsu Provincial Department of Education","doi-asserted-by":"publisher","award":["06200054"],"award-info":[{"award-number":["06200054"]}],"id":[{"id":"10.13039\/501100007166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016692","name":"Key Research and Development Program of Ningxia","doi-asserted-by":"publisher","award":["2021BEG02029"],"award-info":[{"award-number":["2021BEG02029"]}],"id":[{"id":"10.13039\/100016692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is a huge demand for safe and effective non-hormonal male contraceptives to prevent unintended pregnancy, but research on male contraceptive drugs lacks far behind the pills for women. Lonidamine and its analog adjudin are two of the best studied potential male contraceptives. However, the acute toxicity of lonidamine and the subchronic toxicity of adjudin had impeded their development for male contraception. Here, we designed and synthesized a whole new series of molecules derived from lonidamine according to a structure ligand-based design strategy and obtained a new effective and reversible contraceptive agent (BHD), and their efficacy was demonstrated in male mice and rats. Results showed that BHD had a 100% contraceptive effect on male mice after 2 weeks following a single oral dose of BHD at 100 mg\/kg body weight (b.w.) or 500 mg\/kg b.w. treatments. The fertility of mice was reduced to 90 and 50% after 6 weeks with a single oral dose of BHD-100 and BHD-500 mg\/kg b.w. treatments, respectively. We also revealed that BHD induced the apoptosis of spermatogenic cells rapidly and disrupted the blood\u2013testis barrier effectively. It appears to be a new potential male contraceptive candidate for future development.<\/jats:p>","DOI":"10.1021\/acsomega.3c01840","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T04:30:00Z","timestamp":1683865800000},"page":"18245-18254","source":"Crossref","is-referenced-by-count":6,"title":["Discovering a Reversible\nMale Contraceptive Agent\nDerived from Lonidamine"],"prefix":"10.1021","volume":"8","author":[{"given":"Shengnan","family":"Gong","sequence":"first","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2460-7945","authenticated-orcid":true,"given":"Wenqing","family":"Li","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Yao","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Sun","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, P. R. China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"2026081708223017300_cit1","doi-asserted-by":"publisher","first-page":"4113","DOI":"10.4103\/jfmpc.jfmpc_1473_21","article-title":"The Population Control Bill, 2021: Exploring newer\nperspectives","volume":"11","author":"Nagabhushana","year":"2022","journal-title":"J. Family Med. Prim. Care"},{"key":"2026081708223017300_cit2","volume-title":"Oral contraceptive\nuse by formulation and\nbreast cancer risk by subtype in the Nurses\u2019 Health Study II:\na prospective cohort study","author":"Burchardt","year":"2021"},{"key":"2026081708223017300_cit3","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1001\/jama.2021.21392","article-title":"Contraception Selection,\nEffectiveness, and Adverse\nEffects: A Review","volume":"326","author":"Teal","year":"2021","journal-title":"JAMA"},{"key":"2026081708223017300_cit4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1177\/1076029616683802","article-title":"Oral Contraceptives and HRT Risk of Thrombosis","volume":"24","author":"Gialeraki","year":"2018","journal-title":"Clin. Appl. Thromb.\/Hemostasis"},{"key":"2026081708223017300_cit5","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/humrep\/deh574","article-title":"Attitudes\ntoward male fertility control: results of a multinational survey on\nfour continents","volume":"20","author":"Heinemann","year":"2005","journal-title":"Hum. Reprod."},{"key":"2026081708223017300_cit6","doi-asserted-by":"publisher","first-page":"e2381","DOI":"10.1210\/clinem\/dgab034","article-title":"Update\non Novel Hormonal and Nonhormonal\nMale Contraceptive Development","volume":"106","author":"Long","year":"2021","journal-title":"J. Clin. Endocrinol.\nMetab."},{"key":"2026081708223017300_cit7","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.contraception.2012.08.016","article-title":"New approaches to\nmale non-hormonal contraception","volume":"87","author":"Nya-Ngatchou","year":"2013","journal-title":"Contraception"},{"key":"2026081708223017300_cit8","doi-asserted-by":"publisher","first-page":"14715","DOI":"10.1021\/acs.jmedchem.1c01201","article-title":"Blockade\nof GRTH\/DDX25 Phosphorylation by Cyclic Peptides Provides an Avenue\nfor Developing a Nonhormonal Male Contraceptive","volume":"64","author":"Raju","year":"2021","journal-title":"J. Med. Chem."},{"key":"2026081708223017300_cit9","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1093\/oxfordjournals.humrep.a138637","article-title":"Possible\nphysiological bases for contraceptive techniques in the male","volume":"9","author":"Setchell","year":"1994","journal-title":"Hum. Reprod."},{"key":"2026081708223017300_cit10","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1095\/biolreprod65.2.449","article-title":"Two new male\ncontraceptives exert their effects by depleting germ\ncells prematurely from the testis","volume":"65","author":"Cheng","year":"2001","journal-title":"Biol. Reprod."},{"key":"2026081708223017300_cit11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.semcdb.2021.03.024","article-title":"mTORC1\/rpS6 and p-FAK-Y407 signaling regulate spermatogenesis:\nInsights from studies of the adjudin pharmaceutical\/toxicant model","volume":"121","author":"Wang","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"2026081708223017300_cit12","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1530\/REP-10-0464","article-title":"Adjudin,\na potential male contraceptive, exerts its effects locally in the\nseminiferous epithelium of mammalian testes","volume":"141","author":"Mok","year":"2011","journal-title":"Reproduction"},{"key":"2026081708223017300_cit13","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1038\/nm1420","article-title":"A male contraceptive\ntargeting germ cell adhesion","volume":"12","author":"Mruk","year":"2006","journal-title":"Nat. Med."},{"key":"2026081708223017300_cit14","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1095\/biolreprod.106.057810","article-title":"A novel potent indazole carboxylic\nacid derivative blocks spermatogenesis and is contraceptive in rats\nafter a single oral dose","volume":"78","author":"Tash","year":"2008","journal-title":"Biol. Reprod."},{"key":"2026081708223017300_cit15","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1124\/jpet.122.001195","article-title":"Physiological\nCharacterization of the Transporter-Mediated Uptake of the Reversible\nMale Contraceptive H2-Gamendazole Across the Blood-Testis Barrier","volume":"382","author":"Hau","year":"2022","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026081708223017300_cit16","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/cts.12708","article-title":"Development\nof Novel Male Contraceptives","volume":"13","author":"Amory","year":"2020","journal-title":"Clin. Transl.\nSci."},{"key":"2026081708223017300_cit17","first-page":"603","article-title":"Focus: Sex\n& Reproduction: Male\nContraception","volume":"93","author":"Abbe","year":"2020","journal-title":"Yale J. Biol. Med."},{"key":"2026081708223017300_cit18","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1373\/clinchem.2018.295089","article-title":"Male Contraceptive\nDevelopment: Update\non Novel Hormonal and Nonhormonal Methods","volume":"65","author":"Long","year":"2019","journal-title":"Clin.\nChem."},{"key":"2026081708223017300_cit19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000238040","article-title":"Basic and\napplied research in the study of indazole carboxylic acids","volume":"27","author":"Silvestrini","year":"1981","journal-title":"Chemotherapy"},{"key":"2026081708223017300_cit20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1159\/000238043","article-title":"Effects of AF 1312 TS and lonidamine on mammalian testis.\nA morphological study","volume":"27","author":"De\nMartino","year":"1981","journal-title":"Chemotherapy"},{"key":"2026081708223017300_cit21","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aax4067","article-title":"Hexokinase 2 couples glycolysis with the profibrotic\nactions of TGF-\u03b2","volume":"12","author":"Yin","year":"2019","journal-title":"Sci. Signaling"},{"key":"2026081708223017300_cit22","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1074\/jbc.M115.697516","article-title":"Inhibition of Mitochondrial\nComplex II by the Anticancer Agent Lonidamine","volume":"291","author":"Guo","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2026081708223017300_cit23","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.bbcan.2016.08.001","article-title":"Mechanism of antineoplastic activity\nof lonidamine","volume":"1866","author":"Nath","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"2026081708223017300_cit24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060656","article-title":"Rai14 (retinoic\nacid induced protein\n14) is involved in regulating f-actin dynamics at the ectoplasmic\nspecialization in the rat testis","volume":"8","author":"Qian","year":"2013","journal-title":"PLoS One"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.3c01840","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/8\/20\/18245\/4080411\/ao3c01840.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/8\/20\/18245\/4080411\/ao3c01840.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:31Z","timestamp":1786969711000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/8\/20\/18245\/407525\/Discovering-a-Reversible-Male-Contraceptive-Agent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":24,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,5,12]]},"published-print":{"date-parts":[[2023,5,23]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.3c01840","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,12]]}}}