An overview of recent advancements in small molecules suppression of oncogenic signaling of K-RAS: an updated review.

Autor: Sabt A; Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt. as.sabt@nrc.sci.eg., Tawfik HO; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt. haytham.omar.mahmoud@pharm.tanta.edu.eg., Khaleel EF; Department of Medical Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia., Badi RM; Department of Medical Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia., Ibrahim HAA; Pediatric Department, Faculty of Medicine, Cairo University, Cairo, Egypt., Elkaeed EB; Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, 13713, Riyadh, Saudi Arabia., Eldehna WM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, P.O. Box 33516, Egypt. wagdy2000@gmail.com.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2024 Jan 30. Date of Electronic Publication: 2024 Jan 30.
DOI: 10.1007/s11030-023-10777-6
Abstrakt: RAS (rat sarcoma) oncoproteins are crucial for the growth of some human cancers, including lung, colorectal, and pancreatic adenocarcinomas. The RAS family contains three known human isoforms H(Harvey)-RAS, N(Neuroblastoma)-RAS, and K(Kirsten)-RAS. Mutations in RAS proteins cause up to ~ 30% of cancer cases. For almost 30 years, mutant proteins druggable pockets remained undiscovered, they are nearly identical to their essential, wild-type counterparts and cause cancer. Recent research has increased our knowledge of RAS's structure, processing, and signaling pathways and revealed novel insights into how it works in cancer cells. We highlight several approaches that inhibit RAS activity with small compounds in this review: substances that blocked farnesyltransferase (FTase), isoprenylcysteine carboxyl methyltransferase (Icmt), and RAS-converting enzyme 1 (Rce1) three important enzymes required for RAS localization. Inhibitors block the son of sevenless (SOS) protein's role in nucleotide exchange activity, small molecules that interfered with the phosphodiesterase (PDEδ)-mediated intracellular RAS transport processes, substances that focused on inhibiting RAS-effector interactions. Inhibitors are made to suppress the oncogenic K-RAS G12C mutant only when the nucleophilic cysteine residue at codon 12 is present and many inhibitors with various mechanisms like breaking the organization membrane of K-RAS nano-clustering. So, this is a thorough analysis of the most recent advancements in K-RAS-targeted anticancer techniques, hopefully offering insight into the field's future.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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