{"entity": "publication", "iuid": "24c7ee9c1b0f4a1d9ac6cac2bfdf872d", "timestamp": "2026-09-18T08:58:18.417Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/24c7ee9c1b0f4a1d9ac6cac2bfdf872d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/24c7ee9c1b0f4a1d9ac6cac2bfdf872d"}}, "title": "AI-driven discovery and validation of a GIPC1 PDZ domain inhibitor for pancreatic ductal adenocarcinoma.", "authors": [{"family": "Rachamala", "given": "Hari Krishnareddy", "initials": "HK"}, {"family": "Rao Nakka", "given": "Naga Malleswara", "initials": "NM"}, {"family": "Angom", "given": "Ramcharan Singh", "initials": "RS"}, {"family": "Varanasi", "given": "Sai Manasa", "initials": "SM"}, {"family": "Wei", "given": "Fang", "initials": "F"}, {"family": "Kulkarni", "given": "Tanmay", "initials": "T"}, {"family": "Dutta", "given": "Shamit Kumar", "initials": "SK"}, {"family": "Wang", "given": "Enfeng", "initials": "E"}, {"family": "Kulkarni", "given": "Nagaraj M", "initials": "NM"}, {"family": "Geoffrey A S", "given": "Ben", "initials": "B"}, {"family": "Hegde", "given": "Shraddha Prabhakar", "initials": "SP"}, {"family": "Perumal", "given": "Saravanan", "initials": "S"}, {"family": "Gurram", "given": "Kishan", "initials": "K"}, {"family": "Gharibi", "given": "Hassan", "initials": "H"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Mukherjee", "given": "Sourav Pr", "initials": "SP"}, {"family": "Babiker", "given": "Hani", "initials": "H"}, {"family": "Pal", "given": "Krishnendu", "initials": "K"}, {"family": "Mukhopadhyay", "given": "Debabrata", "initials": "D"}], "type": "journal article", "published": "2026-07-31", "journal": {"title": "Cell Rep", "issn": "2211-1247", "pages": "117777", "issn-l": null}, "abstract": "Pancreatic ductal adenocarcinoma (PDAC) remains highly aggressive, with a five-year survival rate under 13.3%, due to late diagnosis, rapid progression, and therapeutic resistance, highlighting the need for advanced treatments. GAIP-interacting protein C terminus 1 (GIPC1), a scaffolding protein overexpressed in PDAC, drives tumor growth and chemoresistance but has remained \"undruggable\" due to its PDZ domain. Using advanced computational modeling, machine learning, and predictive analytics, we identified a selective and specific small molecule inhibitor of GIPC1 (GIPCi) targeting its PDZ domain. Binding of GIPCi with GIPC1 protein itself was confirmed via hydrogen-deuterium exchange mass spectrometry (HDX-MS). Preclinical studies showed that GIPCi alone or in combination with gemcitabine (GEM) significantly suppressed tumor growth and improved survival in PDAC models by blocking key pro-tumorigenic pathways. These findings demonstrate the power of AI-driven drug discovery and rigorous validation in unlocking advanced therapeutic targets for treatment-resistant cancers like PDAC.", "doi": "10.1016/j.celrep.2026.117777", "pmid": "42537645", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S2211-1247(26)00855-7"}], "notes": [], "created": "2026-09-17T12:43:29.664Z", "modified": "2026-09-17T12:43:29.670Z"}