Covalent Inhibition in Drug Discovery.
TLDR
This review surveys enzymes that can be targeted by covalent inhibitors for the treatment of human diseases, focusing on protein kinases, RAS proteins, and a few other enzymes that have been studied extensively as targets for covalents.Abstract:
Although covalent inhibitors have been used as therapeutics for more than a century, there has been general resistance in the pharmaceutical industry against their further development due to safety concerns. This inclination has recently been reverted after the development of a wide variety of covalent inhibitors to address human health conditions along with the US Food and Drug Administration (FDA) approval of several covalent therapeutics for use in humans. Along with this exciting resurrection of an old drug discovery concept, this review surveys enzymes that can be targeted by covalent inhibitors for the treatment of human diseases. We focus on protein kinases, RAS proteins, and a few other enzymes that have been studied extensively as targets for covalent inhibition, with the aim to address challenges in designing effective covalent drugs and to provide suggestions in the area that have yet to be explored.read more
Citations
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In silico Screening of Natural Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike RBD: Targets for COVID-19
TL;DR: In this article, the authors investigated the antiviral action of several groups of phytoconstituents against SARS-CoV-2 using a molecular docking approach to inhibit Main Protease (Mpro) and spike (S) glycoprotein receptor binding domain (RBD) to ACE2 (PDB code: 6M0J), the cause of COVID-19.
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Advances in covalent drug discovery
TL;DR: Covalent drugs have been used to treat diseases for more than a century, but tools that facilitate the rational design of covalent drug have emerged more recently as discussed by the authors , and the purposeful addition of reactive functional groups to existing ligands can enable potent and selective inhibition of target proteins, as demonstrated by the Covalent epidermal growth factor receptor (EGFR) and Bruton's tyrosine kinase (BTK) inhibitors used for treating various cancers.
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Recent Developments in PROTAC-Mediated Protein Degradation: From Bench to Clinic
Zhenyi Hu,Craig M. Crews +1 more
TL;DR: Proteolysis-targeting chimeras (PROTACs), an emerging paradigm-shifting technology, hijacks the ubiquitin-proteasome system for targeted protein degradation.
Journal ArticleDOI
Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression.
Elmira Roshani Asl,Mohammad Amini,Souzan Najafi,Behzad Mansoori,Ahad Mokhtarzadeh,Ali Mohammadi,Parisa Lotfinejad,Mehdi Bagheri,Solmaz Shirjang,Ziba Lotfi,Yousef Rasmi,Behzad Baradaran +11 more
TL;DR: In this article, the interplay between miRNAs and MAPK signaling in various steps of tumorigenesis, including metabolic regulation, cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance, is discussed.
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Fragment-based covalent ligand discovery
Wenchao Lu,Milka Kostic,Tinghu Zhang,Jianwei Che,Matthew P. Patricelli,Lyn H. Jones,Edward T. Chouchani,Nathanael S. Gray +7 more
TL;DR: This work discusses how the two strategies synergize to facilitate the efficient discovery of new pharmacological modulators of established and new therapeutic target proteins.
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