MAC-545496

MAC-545496 is a nanomolar inhibitor of glycopeptide-resistance-associated protein R (GraR). MAC-545496 displays strong binding affinity to the full-length GraR protein (Kd ≤ 0.1 nM). MAC-545496 is an antivirulence agent that reverses β-lactam resistance in Methicillin-resistant strains (MRSA).

Product information

CAS Number: 838810-96-1

Molecular Weight: 419.89

Formula: C18H18ClN5O3S

Chemical Name: 1-(5-chloropyridin-2-yl)-3-[3-nitro-4-(piperidin-1-yl)benzoyl]thiourea

Smiles: [O-][N+](=O)C1=CC(=CC=C1N1CCCCC1)C(=O)NC(=S)NC1=CC=C(Cl)C=N1

InChiKey: AFOKREIUUQFDNW-UHFFFAOYSA-N

InChi: InChI=1S/C18H18ClN5O3S/c19-13-5-7-16(20-11-13)21-18(28)22-17(25)12-4-6-14(15(10-12)24(26)27)23-8-2-1-3-9-23/h4-7,10-11H,1-3,8-9H2,(H2,20,21,22,25,28)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 250 mg/mL (595.39 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

MAC-545496 potently synergizes with Cefuroxime; concentrations as low as 0.03 µg/mL (~75 nM) lowers the β-lactam MIC from 512 to 8 µg/mL against S. aureus USA300. MAC545496 also synergizes with Cefuroxime and Oxacillin against a collection of ten S. aureus clinical isolates. In addition, MAC-545496 potentiates the effect of Cefuroxime against representatives of other circulating MRSA strains such as USA100, USA400 and USA500 to different extents, with the exception of CMRSA4, a USA200/EMRSA16 isolate. MAC-545496 also synergizes with the antimicrobial peptides colistin and polymyxin B. MAC-545496 shows inhibition of mprF expression in a concentration-dependent manner; the IC50 value is 0.0376 µg/mL. MAC-545496 also inhibits the citrateinduced biofilm formation in the wild type in a concentration dependent manner.

In Vivo:

In vivo, MAC-545496 is effective as a monotherapy for MRSA infected Galleria mellonella larvae. MAC-545496 activity is evidenced by increased survival of the drug-treated larvae as compared to infected untreated ones. This corresponded to concentration-dependent killing of S. aureus in the hemolymph of the larvae observed from the CFUs recovered from the hemolymph 200 min after infection. Treatment of S. aureus-infected larvae with MAC-545496 occurred 30min after infection that mimics acquiring bacterial infection before initiating antimicrobial therapy .

Products are for research use only. Not for human use.