Advances in the discovery of activin receptor-like kinase 5 (ALK5) inhibitors

被引：3
作者：
Mansour, Mai A. [1 ]
Hassan, Ghaneya S. [1 ,2 ]
Serya, Rabah A. T. [3 ]
Jaballah, Maiy Y. [3 ]
Abouzid, Khaled A. M. [3 ]
机构：
[1] Badr Univ Cairo, Sch Pharm, Pharmaceut Chem Dept, Cairo, Egypt
[2] Cairo Univ, Fac Pharm, Pharmaceut Chem Dept, Cairo, Egypt
[3] Ain Shams Univ, Fac Pharm, Pharmaceut Chem Dept, Cairo, Egypt
来源：
BIOORGANIC CHEMISTRY | 2024年 / 147卷
关键词：
TGF-beta; ALK5; inhibitors; Binding interactions; Structure-activity relationship; TGF-BETA RECEPTOR; TO-MESENCHYMAL TRANSITION; SMALL-MOLECULE INHIBITOR; I RECEPTOR; BIOLOGICAL EVALUATION; DOMAIN INHIBITORS; POTENT; DESIGN; FIBROSIS; DERIVATIVES;
D O I：
10.1016/j.bioorg.2024.107332
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Activin receptor-like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-beta (TGF-beta) family. (TGF-beta) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK5 inhibitors. In this review, we shed light on the current ATP-competitive inhibitors of ALK5 through diverse heterocyclic based scaffolds that are in clinical or pre-clinical phases of development. Moreover, we focused on the binding interactions of the compounds to the ATP binding site and the structure-activity relationship (SAR) of each scaffold, revealing new scopes for designing novel candidates with enhanced selectivity and metabolic profiles.
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页数：16
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