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Molecular docking was used to identify their binding modes to the biological target GFR\u03b11 in GDNF-binding pocket. Thereafter, commercially available compounds based on the best predicted structures were searched from ZINC and MolPort databases (similarity \u2265 80%). Five compounds from the ZINC library were tested in phosphorylation and luciferase assays to study their ability to activate GFR\u03b11\u2013RET. A bidental compound with two carboxyl groups showed the highest activity in molecular modeling and biological studies. However, the relative position of these groups was important. The meta-substituted structure otherwise identical to the most active compound 2-[4-(5-carboxy-1H-1,3-benzodiazol-2-yl)phenyl]-1H-1,3-benzodiazole-5-carboxylic acid was inactive. A weaker activity was detected for a compound with a single carboxyl group, that is, 4-(1,3-benzoxazol-2-yl)benzoic acid. The substitution of the carboxyl group by the amino or acetamido group also led to the loss of the activity.<\/jats:p>","DOI":"10.1021\/acsomega.7b01932","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T12:22:12Z","timestamp":1516882932000},"page":"1022-1030","source":"Crossref","is-referenced-by-count":20,"title":["Small-Molecule Ligands as Potential GDNF Family Receptor\nAgonists"],"prefix":"10.1021","volume":"3","author":[{"given":"Larisa","family":"Ivanova","sequence":"first","affiliation":[{"name":"University of Tartu , , Ravila 14A , ,","place":["Tartu, Estonia, 50411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaana","family":"Tammiku-Taul","sequence":"additional","affiliation":[{"name":"University of Tartu , , Ravila 14A , ,","place":["Tartu, Estonia, 50411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Sidorova","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, HiLIFE, University of Helsinki , , Viikinkaari 5D , ,","place":["Helsinki, Finland, 00014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart","family":"Saarma","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, HiLIFE, University of Helsinki , , Viikinkaari 5D , ,","place":["Helsinki, Finland, 00014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mati","family":"Karelson","sequence":"additional","affiliation":[{"name":"University of Tartu , , Ravila 14A , ,","place":["Tartu, Estonia, 50411"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,1,25]]},"reference":[{"key":"2026090408105531000_cit1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn812","article-title":"The GDNF family: signalling, biological functions and\ntherapeutic value","volume":"3","author":"Airaksinen","year":"2002","journal-title":"Nat. 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