Utilization of Existing Human Kinase Inhibitors As Scaffolds in the Development of New Antimicrobials
Overview
Overview
Authors
Authors
Affiliations
Affiliations
Soon will be listed here.
Abstract
The prevalence and continuing expansion of drug resistance, both in clinical and community settings represents a major challenge for current antimicrobial therapy. The different approaches for addressing this challenge include (1) identification of novel antibacterials by repurposing of existing drugs originally that historically target host proteins; and (2) effect target switching through modification of existing antimicrobials. The focus of this manuscript is on these drug discovery strategies, with utility for development of new antimicrobials with different modes of action.
References
1.
Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S
. The protein kinase complement of the human genome. Science. 2002; 298(5600):1912-34.
DOI: 10.1126/science.1075762.
View
2.
Kim S, Ko D, Lee Y, Jang S, Lee Y, Lee I
. Anti-cancer activity of the novel 2-hydroxydiarylamide derivatives IMD-0354 and KRT1853 through suppression of cancer cell invasion, proliferation, and survival mediated by TMPRSS4. Sci Rep. 2019; 9(1):10003.
PMC: 6620293.
DOI: 10.1038/s41598-019-46447-7.
View
3.
Pensinger D, Aliota M, Schaenzer A, Boldon K, Ansari I, Vincent W
. Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to β-lactam antibiotics. Antimicrob Agents Chemother. 2014; 58(8):4486-94.
PMC: 4135996.
DOI: 10.1128/AAC.02396-14.
View
4.
Schaenzer A, Wlodarchak N, Drewry D, Zuercher W, Rose W, Ferrer C
. GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus. ACS Infect Dis. 2018; 4(10):1508-1518.
PMC: 6779124.
DOI: 10.1021/acsinfecdis.8b00136.
View
5.
Le P, Kunold E, Macsics R, Rox K, Jennings M, Ugur I
. Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms. Nat Chem. 2019; 12(2):145-158.
PMC: 6994260.
DOI: 10.1038/s41557-019-0378-7.
View