PGE synthase (Prostaglandin E synthase), which converts cyclooxygenase (COX)-derived prostaglandin (PG) H2 to PGE2, occurs in multiple forms with distinct enzymatic properties, modes of expression, cellular and subcellular localizations and intracellular functions. Cytosolic PGES (cPGES) is a cytosolic protein that is constitutively expressed in a wide variety of cells and tissues and is associated with heat shock protein 90 (Hsp90). Membrane-associated PGES (mPGES), the expression of which is stimulus-inducible and is downregulated by anti-inflammatory glucocorticoids, is a perinuclear protein belonging to the microsomal glutathione S-transferase (GST) family. These two PGESs display distinct functional coupling with upstream COXs in cells; cPGES is predominantly coupled with the constitutive COX-1, whereas mPGES is preferentially linked with the inducible COX-2. Several cytosolic GSTs also have the capacity to convert PGH2 to PGE2 in vitro. Accumulating evidence has suggested that mPGES participates in various pathophysiological states in which COX-2 is involved, implying that mPGES represents a potential novel target for drug development.
|Cat. No.||Product Name||CAS No.||Information|
Crisdesalazine (AAD-2004, AAD2004) is a derivative of aspirin that inhibits microsomal PGE(2) synthase-1 (mPGES-1) activity in response to both LPS-treated BV2 cell with IC50 of 230 nM and recombinant human mPGES-1 protein with IC50 of 249 nM in vitro; blocked free radical production, PGE(2) formation, and microglial activation in the spinal cords in superoxide dismutase 1(G93A) transgenic mouse model of ALS, reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span, which is superior to riluzole or ibuprofen.
Pizuglanstat is a potent, selective prostaglandin D synthase inhibitor.
mPGES1-IN-16 is a potent and selective mPGES-1 inhibitor with IC50 of 1 nM; displays no activity against a panel of 35 receptors, ion channels, and hERG; shows IC50/IC80 of 6 nM/24 nM for inhibition of PGE2 formation in vitro in LPS-stimulated human whole blood (HWB); orally bioavailable in vivo.
PF-9184 is a potent, selective mPGES-1 (microsomal prostaglandin E synthase-1) inhibitor with IC50 of 16.5 nM; shows no effect against COX-1 and COX-2 (>6,500-fold selectivity); inhibits PGE2 synthesis in serum-free cell and human whole blood cultures with IC50 of 0.5-5 uM, while sparing the synthesis of PGF(1alpha)) and PGF(2alpha).
hPGDS-IN-1 is a potent, selective hPGDS inhibitor with IC50 of 12 nM in FP or EIA assays.
A locally-acting nonsteroidal anti-inflammatory drug (NSAID) with local anaesthetic and analgesic properties for pain relief and anti-inflammatory treatment of inflammatory conditions; also shows notable in vitro antibacterial activity.
A novel potent (IC50=910 ng/mL), highly selective microsomal prostaglandin E synthase 1 inhibitor (mPGES-1) for treatment of undisclosed indications.
mPGES1-IN-17d is a potent, selective mPGES-1 inhibitor with enzyme IC50 of 8 nM, A549 cell IC50 of 16.24 nM, human whole blood IC50 of 249.9 nM; displays excellent in vitro selectivity over mPGES-2, cPGES, COX1/2, other prostanoid synthases, favorable hERG and CEREP panel profile; shows good efficacy in LPS-induced thermal hyperalgesia pain model; demonstrates good oral pharmacokinetic profiles and good CNS B/P ratio in rat and guinea pig.
MF63 is a potent, selective, and orally active mPGES-1 inhibitor with IC50 of 1.3 nM for human mPGES-1 enzyme, >1000-fold selectivity over other prostanoid synthases; strongly inhibits guinea pig mPGES-1 (IC50= 0.9 nM) but not the mouse or rat enzyme; selectively suppresses the synthesis of PGE(2), but not other prostaglandins inhibitable by NSAIDs, yet retains NSAID-like efficacy at inhibiting LPS-induced pyresis, hyperalgesia, and iodoacetate-induced osteoarthritic pain, relieves pyresis and pain in preclinical models of inflammation.
HPGDS inhibitor 1
HPGDS inhibitor 1 is a potent, selective, oral hematopoietic prostaglandin D synthase (HPGDS) inhibitor with enzyme IC50 of 0.6 nM; does not inhibit human L-PGDS, mPGES, COX-1, COX-2, or 5 LOX (IC50>10 uM); reduces the antigen-induced response in vivo.
No.1378 West Wenyi Road, Yuhang District, HangZhou, Zhejiang, China