A reversible, potent, and selective sPLA2-IIA/PLA2g2a (phospholipase A2 group IIA) inhibitor (IC50 = 29nM) that displays much reduced potency against sPLA2-V/PLA2g5 (PLA2 group V; IC50 = 2uM) and is reported not to affect the activity of cytosolic cPLA2, Ca2+-independent iPLA2, 30 human GPCRs, and 25 other enzymes. In addition to being useful in studying PLA2g2a-mediated cellular responses in cultures in vitro (100% inhibition of LPS-induced PGE2 production in HMC-1 cells; 15 min 10uM pretreatment), KH064 is orally available in rats and efficacious in various rat disease models in vivo (5mg/kg p.o.), including adjuvant-induced arthritis, spontaneous hypertension, high fat diet-induced metabolic disorders. Comparing to the substrate-competitive inhibitor c(2NapA)LS(2NapA)R, KH064 also effectively chelates sPLA2-IIA active site Ca2+ in addition to targeting the enzyme's N-terminal lipid substrate binding site.
Synonyms:(S)-5-(4-(benzyloxy)phenyl)-4-(7-phenylheptanamido)pentanoic acid, Phospholipase A₂ Group IIA Inhibitor II, PLA2g2a Inhibitor II
Formula:C31H37NO4
Solubility:DMSO
Storage and Stability:May be stored at 4°C. For long-term storage, aliquot and store at 4°C. Do not freeze. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.
