{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:13:09Z","timestamp":1791133989453,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T00:00:00Z","timestamp":1246233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2009,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>The cellular protein lens epithelium\u2010derived growth factor, or transcriptional coactivator p75 (LEDGF\/p75), plays a crucial role in HIV integration. The protein\u2013protein interactions (PPIs) between HIV\u20101 integrase (IN) and its cellular cofactor LEDGF\/p75 may therefore serve as targets for the development of new anti\u2010HIV drugs. In this work, a structure\u2010based pharmacophore model for potential small\u2010molecule inhibitors of HIV\u20101 IN\u2013LEDGF\/p75 interaction was developed using the LigandScout software. The 3D model obtained was used for virtual screening of our in\u2010house chemical database, CHIME, leading to the identification of compound CHIBA\u20103002 as an interesting hit for further optimization. The rational design, synthesis and biological evaluation of four derivatives were then carried out. Our studies resulted in the discovery of a new and more potent small molecule (<jats:bold>7<\/jats:bold>, CHIBA\u20103003) that is able to interfere with the HIV\u20101 IN\u2013LEDGF\/p75 interaction at micromolar concentration, representing one of the first compounds to show activity against these specific PPIs. Docking simulations were subsequently performed in order to investigate the possible binding mode of our new lead compound to HIV\u20101 IN. This study is a valid starting point for the identification of anti\u2010HIV agents with a different mechanism of action from currently available antiviral drugs.<\/jats:italic><\/jats:p>","DOI":"10.1002\/cmdc.200900070","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T14:18:12Z","timestamp":1246285092000},"page":"1311-1316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Pharmacophore\u2010Based Discovery of Small\u2010Molecule Inhibitors of Protein\u2013Protein Interactions between HIV\u20101 Integrase and Cellular Cofactor LEDGF\/p75"],"prefix":"10.1002","volume":"4","author":[{"given":"Laura","family":"De\u2005Luca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Letizia","family":"Barreca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Ferro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Christ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzio","family":"Iraci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Gitto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Monforte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeger","family":"Debyser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Chimirri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,30]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.12.002"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.07.139"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1039\/b810306b"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.09.005"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.03.089"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.10.094"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.08.003"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506924102"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.02.076"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci600320q"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm050549e"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0897"},{"key":"e_1_2_6_13_2","unstructured":"The PyMOL Molecular Graphics System W.\u2005L. DeLano DeLano Scientific LLC San Carlos CA (USA) 2008;http:\/\/www.pymol.org."},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci049885e"},{"key":"e_1_2_6_15_2","unstructured":"Catalyst\u20054.10 Accelrys Software Inc. San Diego CA (USA);http:\/\/www.accelrys.com."},{"key":"e_1_2_6_16_2","unstructured":"SYBYL\u20058.0 Tripos Inc. St.\u2009Louis MO (USA) 2005."},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm8009266"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.200900070","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.200900070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:51:51Z","timestamp":1760305911000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.200900070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,30]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2009,8,3]]}},"alternative-id":["10.1002\/cmdc.200900070"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.200900070","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,30]]},"assertion":[{"value":"2009-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-07-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}