Walrycin B

• CAT Number: I005285
• CAS Number: 878419-78-4
• Molecular Formula: C14H10F3N5O2
• Molecular Weight: 337.30
• Purity: ≥95%
• Synonyms: 1,6-dimethyl-3-(4-(trifluoromethyl)phenyl)pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
• Target: Bacterial; Antibiotic
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IC50: 0.39 ug/ml (MIC for B. subtilis 168); 3.13 ug/ml (MIC for S. aureus N315)
• IUPAC Name: 1,6-dimethyl-3-[4-(trifluoromethyl)phenyl]pyrimido[5,4-e][1,2,4]triazine-5,7-dione
• InChI: InChI=1S/C14H10F3N5O2/c1-21-12(23)9-11(19-13(21)24)22(2)20-10(18-9)7-3-5-8(6-4-7)14(15,16)17/h3-6H,1-2H3
• InChIKey: XRVMPTWWKLKLPB-UHFFFAOYSA-N
• SMILES: CN1C2=NC(=O)N(C(=O)C2=NC(=N1)C3=CC=C(C=C3)C(F)(F)F)C

Walrycin B（Cat No.:I005285）is a small-molecule inhibitor identified for its potential in antibacterial therapy, particularly against pathogens involved in biofilm formation. It works by targeting bacterial ClpXP protease, a crucial protein complex involved in stress response and protein quality control within bacterial cells. By inhibiting ClpXP, Walrycin B disrupts protein homeostasis, leading to bacterial cell death. Its unique mechanism offers a promising approach for combating resistant bacterial strains, making it valuable in research for developing novel treatments targeting persistent infections and biofilm-associated bacteria in clinical settings.

Reference

[1]. Gotoh Y, et al. Novel antibacterial compounds specifically targeting the essential WalR response regulator. J Antibiot (Tokyo). 2010 Mar;63(3):127-34.
Abstract
The WalK/WalR (YycG/YycF) two-component system, which is essential for cell viability, is highly conserved and specific to low-GC percentage of Gram-positive bacteria, making it an attractive target for novel antimicrobial compounds. Recent work has shown that WalK/WalR exerts an effect as a master regulatory system in controlling and coordinating cell wall metabolism with cell division in Bacillus subtilis and Staphylococcus aureus. In this paper, we develop a high-throughput screening system for WalR inhibitors and identify two novel inhibitors targeting the WalR response regulator (RR): walrycin A (4-methoxy-1-naphthol) and walrycin B (1,6-dimethyl-3-[4-(trifluoromethyl)phenyl]pyrimido[5,4-e][1,2,4]triazine-5,7-dione). Addition of these compounds simultaneously affects the expression of WalR regulon genes, leading to phenotypes consistent with those of cells starved for the WalK/WalR system and having a bactericidal effect. B. subtilis cells form extremely long aseptate filaments and S. aureus cells form large aggregates under these conditions. These results show that walrycins A and B are the first antibacterial agents targeting WalR in B. subtilis and S. aureus.