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In this work, using <jats:italic>Tg<\/jats:italic>CDPK1 as drug target, we design a method to discover new inhibitors for CDPK1 as potential drug lead for toxoplasmosis with novel scaffolds based on the combination of 2D\/3D\u2010QSAR and scaffold\u2010hopping methods. All the binding sites of the potential inhibitors were checked by docking method, and only the ones that docked to the most conserved sites of <jats:italic>Tg<\/jats:italic>CDPK1, which make them have less probability to get drug resistance, were remained. As a result, 10 potential inhibitors within two new scaffolds were discovered for <jats:italic>Tg<\/jats:italic>CDPK1 with experimentally verified inhibitory activities in micromole level. The discovery of these inhibitors may contribute to the drug development for toxoplasmosis. Besides, the pipeline which is composed in this work as the combination of QSAR and scaffold\u2010hopping is simple, easy to repeat for researchers without need of in\u2010depth knowledge of pharmacology to get inhibitors with novel scaffolds, which will accelerate the procedure of drug discovery and contribute to the drug repurposing study.<\/jats:p>","DOI":"10.1111\/cbdd.13603","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T15:18:10Z","timestamp":1566487090000},"page":"476-484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of potential <i>Toxoplasma gondii<\/i> CDPK1 inhibitors with new scaffolds based on the combination of QSAR and scaffold\u2010hopping method with in vitro validation"],"prefix":"10.1111","volume":"95","author":[{"given":"Pengyi","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Chemistry and Chemical Engineering Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lipei","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafei","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Burn Orthopedics Lanzhou University Second Hospital Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy First Hospital of Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruizhi","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximing","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute Chinese Academy of Sciences Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxi","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-0173","authenticated-orcid":false,"given":"Xiaojun","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingfeng","family":"Lan","sequence":"additional","affiliation":[{"name":"National Demonstration Centre for Experimental Chemistry Education Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7028-4166","authenticated-orcid":false,"given":"Shuyan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Lanzhou University Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"issue":"3","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1021\/ci00063a011","article-title":"Molecular\u2010identification number for substructure searches","volume":"29","author":"Burden F. 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