Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis
Abstract Endometriosis affects over 190 million women globally, and effective therapies are urgently needed to address the burden of endometriosis on women's health. Using an artificial intelligence (AI)‐driven target discovery platform, two unreported therapeutic targets, guanylate‐binding pro...
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| Format: | Article |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406565 |
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| author | Bonnie Hei Man Liu Yuezhen Lin Xi Long Sze Wan Hung Anna Gaponova Feng Ren Alex Zhavoronkov Frank W. Pun Chi Chiu Wang |
| author_facet | Bonnie Hei Man Liu Yuezhen Lin Xi Long Sze Wan Hung Anna Gaponova Feng Ren Alex Zhavoronkov Frank W. Pun Chi Chiu Wang |
| author_sort | Bonnie Hei Man Liu |
| collection | DOAJ |
| description | Abstract Endometriosis affects over 190 million women globally, and effective therapies are urgently needed to address the burden of endometriosis on women's health. Using an artificial intelligence (AI)‐driven target discovery platform, two unreported therapeutic targets, guanylate‐binding protein 2 (GBP2) and hematopoietic cell kinase (HCK) are identified, along with a drug repurposing target, integrin beta 2 (ITGB2) for the treatment of endometriosis. GBP2, HCK, and ITGB2 are upregulated in human endometriotic specimens. siRNA‐mediated knockdown of GBP2 and HCK significantly reduced cell viability and proliferation while stimulating apoptosis in endometrial stromal cells. In subcutaneous and intraperitoneal endometriosis mouse models, siRNAs targeting GBP2 and HCK notably reduced lesion volume and weight, with decreased proliferation and increased apoptosis within lesions. Both subcutaneous and intraperitoneal administration of Lifitegrast, an approved ITGB2 antagonist, effectively suppresses lesion growth. Collectively, these data present Lifitegrast as a previously unappreciated intervention for endometriosis treatment and identify GBP2 and HCK as novel druggable targets in endometriosis treatment. This study underscores AI's potential to accelerate the discovery of novel drug targets and facilitate the repurposing of treatment modalities for endometriosis. |
| format | Article |
| id | doaj-art-989c8f9cbb534432b214ad0dacf2cb90 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-989c8f9cbb534432b214ad0dacf2cb902025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202406565Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for EndometriosisBonnie Hei Man Liu0Yuezhen Lin1Xi Long2Sze Wan Hung3Anna Gaponova4Feng Ren5Alex Zhavoronkov6Frank W. Pun7Chi Chiu Wang8Insilico Medicine Hong Kong Ltd. Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park Hong Kong ChinaDepartment of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong ChinaInsilico Medicine Hong Kong Ltd. Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park Hong Kong ChinaDepartment of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong ChinaInsilico Medicine Hong Kong Ltd. Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park Hong Kong ChinaInsilico Medicine Shanghai Ltd. 9F, Chamtime Plaza Block C, Lane 2889, Jinke Road, Pudong New Area Shanghai 201203 ChinaInsilico Medicine Hong Kong Ltd. Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park Hong Kong ChinaInsilico Medicine Hong Kong Ltd. Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park Hong Kong ChinaDepartment of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong ChinaAbstract Endometriosis affects over 190 million women globally, and effective therapies are urgently needed to address the burden of endometriosis on women's health. Using an artificial intelligence (AI)‐driven target discovery platform, two unreported therapeutic targets, guanylate‐binding protein 2 (GBP2) and hematopoietic cell kinase (HCK) are identified, along with a drug repurposing target, integrin beta 2 (ITGB2) for the treatment of endometriosis. GBP2, HCK, and ITGB2 are upregulated in human endometriotic specimens. siRNA‐mediated knockdown of GBP2 and HCK significantly reduced cell viability and proliferation while stimulating apoptosis in endometrial stromal cells. In subcutaneous and intraperitoneal endometriosis mouse models, siRNAs targeting GBP2 and HCK notably reduced lesion volume and weight, with decreased proliferation and increased apoptosis within lesions. Both subcutaneous and intraperitoneal administration of Lifitegrast, an approved ITGB2 antagonist, effectively suppresses lesion growth. Collectively, these data present Lifitegrast as a previously unappreciated intervention for endometriosis treatment and identify GBP2 and HCK as novel druggable targets in endometriosis treatment. This study underscores AI's potential to accelerate the discovery of novel drug targets and facilitate the repurposing of treatment modalities for endometriosis.https://doi.org/10.1002/advs.202406565artificial intelligencedrug repurposingendometriosisGBP2HCKITGB2 |
| spellingShingle | Bonnie Hei Man Liu Yuezhen Lin Xi Long Sze Wan Hung Anna Gaponova Feng Ren Alex Zhavoronkov Frank W. Pun Chi Chiu Wang Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis Advanced Science artificial intelligence drug repurposing endometriosis GBP2 HCK ITGB2 |
| title | Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis |
| title_full | Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis |
| title_fullStr | Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis |
| title_full_unstemmed | Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis |
| title_short | Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis |
| title_sort | utilizing ai for the identification and validation of novel therapeutic targets and repurposed drugs for endometriosis |
| topic | artificial intelligence drug repurposing endometriosis GBP2 HCK ITGB2 |
| url | https://doi.org/10.1002/advs.202406565 |
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