Protein Conjugates of SH3-Domain Ligands and ATP-Competitive Inhibitors as Bivalent Inhibitors of Protein Kinases

ChemBioChem ◽  
2009 ◽  
Vol 10 (15) ◽  
pp. 2445-2448 ◽  
Author(s):  
Rakesh Tiwari ◽  
Keykavous Parang
Keyword(s):  
Protein Kinases ◽  
Sh3 Domain ◽  
Protein Conjugates ◽  
Competitive Inhibitors ◽  
Bivalent Inhibitors

scholarly journals Bivalent inhibitors of protein kinases

2014 ◽  
Vol 49 (2) ◽  
pp. 102-115 ◽  
Author(s):  
Carrie M. Gower ◽  
Matthew E. K. Chang ◽  
Dustin J. Maly
Keyword(s):  
Protein Kinases ◽  
Bivalent Inhibitors

Occupational hazards: allosteric regulation of protein kinases through the nucleotide-binding pocket

2011 ◽  
Vol 39 (2) ◽  
pp. 472-476 ◽  
Author(s):  
Angus J.M. Cameron
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Binding Pocket ◽  
Occupational Hazards ◽  
Kinase C ◽  
Competitive Inhibitors ◽  
Central Activity ◽  
Pkc Protein Kinase C ◽  
Significant Opportunity

Targeting the protein kinase ATP-binding pocket provides a significant opportunity for the treatment of disease. Recent studies have revealed a central activity-independent role for nucleotide pocket occupation in the allosteric behaviour of diverse kinases. Regulation of nucleotide pocket conformation with either nucleotides or ATP competitive inhibitors has revealed an added dimension to the targeting of kinases. In the present paper, using PKC (protein kinase C) as a paradigm, the liabilities and opportunities associated with the occupation of the nucleotide pocket are explored.

scholarly journals Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1977
Author(s):  
Eleanor L. Atkinson ◽  
Jessica Iegre ◽  
Paul D. Brear ◽  
Elizabeth A. Zhabina ◽  
Marko Hyvönen ◽  
...  
Keyword(s):  
Protein Kinases ◽  
The Novel ◽  
Chemical Probes ◽  
Alternative Strategies ◽  
Competitive Inhibitors ◽  
Coronavirus Infection ◽  
Selective Chemical ◽  
Novel Coronavirus ◽  
Kinase Ck2

Protein kinases are a large class of enzymes with numerous biological roles and many have been implicated in a vast array of diseases, including cancer and the novel coronavirus infection COVID-19. Thus, the development of chemical probes to selectively target each kinase is of great interest. Inhibition of protein kinases with ATP-competitive inhibitors has historically been the most widely used method. However, due to the highly conserved structures of ATP-sites, the identification of truly selective chemical probes is challenging. In this review, we use the Ser/Thr kinase CK2 as an example to highlight the historical challenges in effective and selective chemical probe development, alongside recent advances in the field and alternative strategies aiming to overcome these problems. The methods utilised for CK2 can be applied to an array of protein kinases to aid in the discovery of chemical probes to further understand each kinase’s biology, with wide-reaching implications for drug development.

A Chemical Genetic Method for Generating Bivalent Inhibitors of Protein Kinases

2009 ◽  
Vol 131 (19) ◽  
pp. 6686-6688 ◽  
Author(s):  
Zachary B. Hill ◽  
B. Gayani K. Perera ◽  
Dustin J. Maly
Keyword(s):  
Protein Kinases ◽  
Genetic Method ◽  
Chemical Genetic ◽  
Bivalent Inhibitors

scholarly journals The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 153 ◽  
Author(s):  
Maciej Masłyk ◽  
Monika Janeczko ◽  
Aleksandra Martyna ◽  
Sławomir Czernik ◽  
Małgorzata Tokarska-Rodak ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Kinases ◽  
Zebrafish Embryos ◽  
Compound I ◽  
Force Microscopy ◽  
Atomic Force ◽  
Multiple Protein ◽  
Competitive Inhibitors ◽  
Reversible Protein Phosphorylation ◽  
Anti Fungal

Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.

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