Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies

Abstract

Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising therapeutic target for treating various cancers (such as breast cancer, liver cancer, etc.) and other diseases (blood diseases, cardiovascular diseases, etc.), owing to its observed overexpression, thereby presenting significant opportunities in drug development. Since its discovery in 2004, extensive research has been conducted on LSD1 inhibitors, with notable contributions from computational approaches. This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Computational techniques, such as virtual screening, molecular docking and 3D-QSAR models, have played a pivotal role in elucidating the interactions between these inhibitors and LSD1. Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information for advancing further research on LSD1 inhibitors.

Targeted Screening of Curcumin Derivatives as Pancreatic Lipase Inhibitors Using Computer-Aided Drug Design

“…It enabled structure-based or ligand-based drug design, encompassing methods such as molecular docking, molecular dynamics simulations, pharmacophore model screening, and molecular property prediction. , Compared with conventional methods of drug development, CADD demonstrated significant advantages in terms of shortened development cycles and cost savings. CADD played an essential role in the design of antimicrobial, antiviral, and anticancer drugs, among others, enhancing its application prospects. ,, The study utilized CADD to conduct molecular docking and property prediction evaluations of curcumin derivatives. In addition to assessing the pancreatic lipase activity and drug-likeness of curcumin derivatives, this method also simulated the dissolution, absorption, binding, and potential side effects upon oral administration of the curcumin derivatives, screening curcumin derivatives that met the desired expectations while closely mimicking the physiological conditions within the body.…”

“…CADD was a technique that utilizes computer-based virtual analysis to study the activity and physicochemical properties of drugs . It enabled structure-based or ligand-based drug design, encompassing methods such as molecular docking, molecular dynamics simulations, pharmacophore model screening, and molecular property prediction. , Compared with conventional methods of drug development, CADD demonstrated significant advantages in terms of shortened development cycles and cost savings. CADD played an essential role in the design of antimicrobial, antiviral, and anticancer drugs, among others, enhancing its application prospects. ,, The study utilized CADD to conduct molecular docking and property prediction evaluations of curcumin derivatives.…”

“… 34 It enabled structure-based or ligand-based drug design, encompassing methods such as molecular docking, molecular dynamics simulations, pharmacophore model screening, and molecular property prediction. 15 , 35 Compared with conventional methods of drug development, CADD demonstrated significant advantages in terms of shortened development cycles and cost savings. CADD played an essential role in the design of antimicrobial, antiviral, and anticancer drugs, among others, enhancing its application prospects.…”

“…CADD played an essential role in the design of antimicrobial, antiviral, and anticancer drugs, among others, enhancing its application prospects. 15 , 35 , 36 The study utilized CADD to conduct molecular docking and property prediction evaluations of curcumin derivatives. In addition to assessing the pancreatic lipase activity and drug-likeness of curcumin derivatives, this method also simulated the dissolution, absorption, binding, and potential side effects upon oral administration of the curcumin derivatives, screening curcumin derivatives that met the desired expectations while closely mimicking the physiological conditions within the body.…”

“…With the rapid advancement of artificial intelligence, computer-aided drug design (CADD) screening holds the potential to significantly reduce the substantial costs associated with conventional drug development . It can predict, screen, and lead optimize compounds based on their structure or potential pharmacological groups. , Based on its primary focus on compound structures and the screening properties related to target receptors, CADD enables seamless alignment with the property alterations resulting from the structural modifications of curcumin . The application of CADD enables high-throughput screening of various distinct characteristics arising from structural modifications of curcumin derivatives.…”