TST1N-224 is a potent response regulator VraRC inhibitor. TST1N-224 can disrupt VraRC-DNA complex formation ( IC 50 =60.2 μM). TST1N-224 exhibits interference with VraRC binding to its cognate DNA through a fast-on-fast-off binding mechanism (K D =23.4 μM). TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR. TST1N-224 inhibits the growths of S. aureus (SA; MIC>126 μM), Methicillin-resistant S. aureus (MRSA; MIC>126 μM), and Vancomycin -intermediate S. aureus (VISA; MIC=63 μM). TST1N-224, an antimicrobial agent, evidently enhances the susceptibility of VISA to both Vancomycin ( HY-B0671 ) and Methicillin ( HY-B0974 ).
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