Targeting protein-protein interactions in drug discovery: Modulators approved or in clinical trials for cancer treatment
- Pharmacol Res. 2025 Jan:211:107544. doi: 10.1016/j.phrs.2024.107544.
- 1. Unitat Mixta de Recerca en Medicina Genòmica, Universitat Autònoma de Barcelona (UAB)-IR SANT PAU, Barcelona, Spain; Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CIBERER, ISCIII), Madrid, Spain.
- 2. Unitat Mixta de Recerca en Medicina Genòmica, Universitat Autònoma de Barcelona (UAB)-IR SANT PAU, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CIBERER, ISCIII), Madrid, Spain.
- 3. CIBERER-ISCIII, IdiPAZ-CNIO Translational Research Unit in Pediatric Hemato-Oncology, La Paz University Hospital Research Institute; Spanish National Cancer Center, Madrid, Spain; Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
- 4. Unitat Mixta de Recerca en Medicina Genòmica, Universitat Autònoma de Barcelona (UAB)-IR SANT PAU, Barcelona, Spain; Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CIBERER, ISCIII), Madrid, Spain; Servei de Genètica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Spain. Electronic address: [email protected].
Protein-protein interactions (PPIs) form complex cellular networks fundamental to many key biological processes, including signal transduction, cell proliferation and DNA repair. In consequence, their perturbation is often associated with many human diseases. Targeting PPIs offers a promising approach in drug discovery and ongoing advancements in this field hold the potential to provide highly specific therapies for a wide range of complex diseases. Despite the development of PPI modulators is challenging, advances in the genetic, proteomic and computational level have facilitated their discovery and optimization. Focusing on Anticancer drugs, in the last years several PPI modulators have entered clinical trials and venetoclax, which targets Bcl-2 Family proteins, has been approved for treating different types of leukemia. This review discusses the clinical development status of drugs modulating several PPIs, such as MDM2-4/p53, HSP90/HSP90, HSP90/CDC37, c-Myc/Max, KRAS/SOS1, CCR5/CCL5, CCR2/CCL2 or Smac/XIAP, in Cancer drug discovery.