Unravelling the target landscape of tranylcypromines for new drug discovery.
10.1016/j.apsb.2025.04.012
- Author:
Yihui SONG
1
;
Junbiao CHANG
2
;
Bin YU
3
Author Information
1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
2. College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China.
3. Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou 450001, China.
- Publication Type:Review
- Keywords:
Amine oxidase;
Cytochrome P450 superfamily;
Human immunodeficiency virus type 1;
New drug discovery;
Platelet P2Y12 receptor;
Privileged scaffold;
Target space;
Tranylcypromine
- From:
Acta Pharmaceutica Sinica B
2025;15(6):2985-3007
- CountryChina
- Language:English
-
Abstract:
Molecular editing around privileged scaffolds, also known as periphery editing, is a commonly used strategy in contemporary drug discovery and development. Tranylcypromine (TCP) is a widely acknowledged scaffold with diverse pharmacological activities. TCP-derived compounds target different enzymes and cellular receptors such as amine oxidase, platelet P2Y12 receptor, and cytochrome P450 superfamily. These compounds have demonstrated various effects including antidepressant, anticancer, antiviral properties, involvement in prostaglandin synthesis, and mediation of drug metabolism. Notably, the first reversible oral P2Y12 receptor antagonist, ticagrelor, is currently used to prevent future myocardial infarction, stroke, and cardiovascular death. Several TCP-based lysine demethylase 1 (LSD1) inhibitors are currently undergoing clinical assessment. MIV-150, a third-generation non-nucleoside reverse transcriptase inhibitor, has progressed to the clinical stage for treating human immunodeficiency virus type 1 (HIV-1) seronegative patients suffering from acute coronary syndrome. This review aims to explore the target landscape of TCPs, highlight key structure-activity relationships (SARs), and emphasize the therapeutic potential of TCPs for treating various diseases. Finally, the lessons learned from our medicinal chemistry practice, challenges and future directions of TCP-based drug discovery are briefly discussed.
