2026-10-21T16:44:51Z https://lifeofresearch.com/oai2

oai:lifeofresearch.com:123 2026-10-21T10:34:33Z type:article openaire

Medicinal Chemistry aliezzat hammam11 Title: Medicinal Chemistry and Cancer: From Molecular Design to Modern Therapeutics Author: Ali Ezzat Hammam Mohamead Medicinal chemistry is at the core of anticancer drug discovery, bridging organic chemistry, molecular biology, and computational informatics. This research provides a comprehensive overview of the principles governing drug design, including Structure-Activity Relationship (SAR), ADMET optimization, pharmacophore modeling, and the emerging concept of the informacophore - the minimal structural and informational features required for biological activity. Cancer is defined by ten hallmarks described by Hanahan and Weinberg (2000, updated 2011 and 2022), including sustained proliferative signaling, evasion of growth suppression, resistance to cell death, and immune evasion. These hallmarks translate into druggable molecular pathways such as EGFR/RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, and p53/MDM2. The review classifies FDA-approved anticancer agents (2015-2026) based on the recent RSC Advances analysis. It covers (i) classical cytotoxics, (ii) targeted kinase inhibitors such as osimertinib and KRAS G12C inhibitors sotorasib and adagrasib, (iii) Antibody-Drug Conjugates (ADCs) like datopotamab deruxtecan (Datroway, approved Jan 2025) and trastuzumab deruxtecan, (iv) Proteolysis-Targeting Chimeras (PROTACs) e.g., CBPD-409 and ERD-1233, and (v) immune checkpoint inhibitors (PD-1/PD-L1) and CAR-T cell therapies. A special focus is given to the landmark FDA approval of daraxonrasib (Rasonque) on August 26, 2026, the first broad RAS(ON) multi-selective inhibitor for metastatic pancreatic adenocarcinoma. In the phase 3 RASolute 302 trial (n=500), it improved median overall survival from 6.7 to 13.2 months (HR 0.40) and PFS from 3.6 to 7.2 months. The report concludes that future directions lie in AI-driven generative chemistry (Chemistry42, GENTRL), degrader-antibody conjugates (DACs), covalent-reversible inhibitors to overcome resistance, and radiotheranostics, marking a definitive shift toward precision and personalized oncology. Keywords: Medicinal Chemistry, SAR, ADC, PROTAC, KRAS, EGFR, Immunotherapy, Daraxonrasib, Drug Design Life of Research 2026-10-21 info:eu-repo/semantics/article https://lifeofresearch.com/articles/123 eng https://lifeofresearch.com/articles/123/files/125/Medicinal_Chemistry_Cancer_Review_Ali_Ezzat-2.pdf application/pdf https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess