YM 26734 (CAS 144337-18-8)
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YM 26734 is a potent inhibitor of secreted phospholipase A2 (sPLA2) group IIA, identified through the optimization of analogs. It competitively inhibits sPLA2 enzymes across various species, demonstrating low nanomolar potency. Specifically, YM 26734 inhibits sPLA2-hGIIA, -mGIIA, -rGIIA, -hGV, -mGV, -hGX, and -mGX with IC50 values ranging from 30 nM to over 1600 nM, depending on the enzyme subtype. The compound exhibits minimal activity against cytosolic PLA2, COX, and lipoxygenase, thus showing specificity towards sPLA2s. The inhibitory mechanism of YM 26734 involves binding to the conserved active site of sPLA2s, which includes a Ca2+ binding loop and an Asp-His catalytic dyad, essential for the enzyme′s activity. This binding interaction is thought to mimic bidentate ligand coordination to metals, including calcium, thereby inhibiting the enzyme′s function. Simplified analogs based on the didodecanoylphloroglucinol portion of YM-26734, which contains the predicted active site calcium-binding group, have also shown potent inhibition at low nanomolar concentrations.
YM 26734 (CAS 144337-18-8) References
- Induction of distinct sets of secretory phospholipase A(2) in rodents during inflammation. | Hamaguchi, K., et al. 2003. Biochim Biophys Acta. 1635: 37-47. PMID: 14642775
- Phospholipase A2 inhibitors in development. | Tibes, U. and Friebe, WG. 1997. Expert Opin Investig Drugs. 6: 279-98. PMID: 15989628
- The first potent inhibitor of mammalian group X secreted phospholipase A2: elucidation of sites for enhanced binding. | Smart, BP., et al. 2006. J Med Chem. 49: 2858-60. PMID: 16686528
- Biochemistry and physiology of mammalian secreted phospholipases A2. | Lambeau, G. and Gelb, MH. 2008. Annu Rev Biochem. 77: 495-520. PMID: 18405237
- Simplified YM-26734 inhibitors of secreted phospholipase A2 group IIA. | Oslund, RC., et al. 2008. Bioorg Med Chem Lett. 18: 5415-9. PMID: 18818074
- Hydrogen sulphide induces mouse paw oedema through activation of phospholipase A2. | di Villa Bianca, Rd., et al. 2010. Br J Pharmacol. 161: 1835-42. PMID: 20825409
- The application of rational design on phospholipase A(2) inhibitors. | Mouchlis, VD., et al. 2011. Curr Med Chem. 18: 2566-82. PMID: 21568891
- Specific roles for Group V secretory PLA₂ in retinal iron-induced oxidative stress. Implications for age-related macular degeneration. | Rodríguez Diez, G., et al. 2013. Exp Eye Res. 113: 172-81. PMID: 23791636
- Dopaminergic Neurons Respond to Iron-Induced Oxidative Stress by Modulating Lipid Acylation and Deacylation Cycles. | Sánchez Campos, S., et al. 2015. PLoS One. 10: e0130726. PMID: 26076361
- Effects of Phospholipase A2 Inhibitors on Bilayer Lipid Membranes. | Dubinin, MV., et al. 2016. J Membr Biol. 249: 339-47. PMID: 26762382
- Regulatory Functions of Phospholipase A2. | Murakami, M., et al. 2017. Crit Rev Immunol. 37: 127-195. PMID: 29773019
- Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice. | Retamal, JS., et al. 2021. Lab Invest. 101: 851-864. PMID: 33859334
- Exogenous group II phospholipase A2 induces prostaglandin E2 production in mouse peritoneal macrophages. | Miyake, A., et al. 1994. Eur J Pharmacol. 253: 155-61. PMID: 8013541
- Suppression of inflammatory responses to 12-O-tetradecanoyl-phorbol-13-acetate and carrageenin by YM-26734, a selective inhibitor of extracellular group II phospholipase A2. | Miyake, A., et al. 1993. Br J Pharmacol. 110: 447-53. PMID: 8220906
Ordering Information
| Product Name | Catalog # | UNIT | Price | Qty | FAVORITES | |
YM 26734, 10 mg | sc-204410 | 10 mg | $224.00 |