HPGDS inhibitor 3 is an orally active and highly potent peripherally restricted hematopoietic prostaglandin D synthase (H-PGDS) inhibitor with IC50 value of 9.4 nM and EC50 of 42 nM. HPGDS inhibitor 3 exhibits good selectivity, good pharmacokinetic parameters in mouse, rat, and dog, and no CNS toxicity. HPGDS inhibitor 3 has anti-inflammatory activity[1].
AT-56 is a potent, selective and orally active inhibitor of lipocalin-type prostaglandin D synthase (L-PGDS), with an IC50 of 95 μM and Ki of 75 μM. AT-56 could selectively suppress the drowsiness or pain reaction mediated by L-PGDS-catalyzed PGD2[1].
Clopirac is a potent and orally active inhibitor of prostaglandin synthetase. Clopirac is an anti-inflammatory agent[1].
HPGDS inhibitor 1 is a novel and selective Hematopoietic Prostaglandin D Synthase (HPGDS) inhibitor with an IC50 Value of 0.7 nM.IC50 Value: 0.7 nM [1]Target: HPGDSHPGDS inhibitor 1 was elected for further profiling based on its enzyme and cell potency. The compound illustrated equal potency against purified HPGDS from human , rat, dog, and sheep (IC50, 0.5-2.3 nM). HPGDS inhibitor 1 was profiled in a panel of cellular assays to screen for activity against several relevant human enzyme targets. Those assay indicated that HPGDS inhibitor 1 does not inhibit human L- PGDS, m-PGDS, COX-1, COX-2 or 5 LOX (IC50 values > 10000 nM).HPGDS inhibitor 1 had a solubility of 1.5 ug/ml (3.9 uM) at pH 6.5. The compound had excellent PK characteristics when dosed in rats at 1 mpk with 76% bioavailavility. Rats dosed orally with 1 and 10 mpk HPGDS inhibitor 1 were sacrificed at various times, and plasma concentrations of HPGDS inhibitor 1 and spleen PGD2 concentrations were measured. Oral administration of HPGDS inhibitor 1 blocked PGD2 production in the rat spleen; inhibition of PGD2 was inversely correlated with the plasma concentration of HPGDS inhibitor 1 in a time and dose-dependent manner. Spleen PGD2 levels fall as HPGDS inhibitor 1 plasma levels increase over time; PGD2 levels return to baseline levels as HPGDS inhibitor 1 plasma levels decline.
Dehydroevodiamine is a major bioactive quinazoline alkaloid isolated from Evodiae Fructus, has an antiarrhythmic effect in guinea-pig ventricular myocytes[1]. Dehydroevodiamine inhibits LPS-induced iNOS, COX-2, prostaglandin E2 (PGE2) and nuclear factor-kappa B (NF-κB) expression in murine macrophage cells[2].
TFC-007, a selective hematopoietic prostaglandin D synthase (H-PGDS) inhibitor, show high inhibitory activity against H-PGDS enzyme (IC50 value of 83 nM). TFC-007 can be used for composing H-PGDS degradation inducer PROTAC(H-PGDS)-1 (TFC-007 binds to H-PGDS, and Pomalidomide binds to cereblon)[1].
Flurbiprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with antipyretic and analgesic activity.Target: PGE synthaseFlurbiprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with antipyretic and analgesic activity. Oral formulations of flurbiprofen may be used for the symptomatic treatment of rheumatoid arthritis, osteoarthritis and anklylosing spondylitis. Flurbiprofen may also be used topically prior to ocular surgery to prevent or reduce intraoperative miosis. Flurbiprofen is structurally and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen. Flurbiprofen may have unique pharmacological properties that reduce the accumulation of unfolded proteins and may represent a new class of drug for the fundamental treatment of obesity [1]. Flurbiprofen and its enantiomers selectively lower Aβ42 levels in broken cell γ-secretase assays, indicating that these compounds directly target the γ-secretase complex that generates Aβ from APP. Of the compounds tested, meclofenamic acid, racemic flurbiprofen, and the purified R and S enantiomers of flurbiprofen lowered Aβ42 levels to the greatest extent [2].
Cafestol, one of the major components of coffee, is a coffee-specific diterpene from. Cafestol is a ERK inhibitor for AP-1-targeted activity against PGE2 production and the mRNA expression of cyclooxygenase (COX)-2 in LPS-activated RAW264.7 cells. Cafestol has strong inhibitory activity on PGE2 production by suppressing the NF-kB activation pathway. Cafestol contributes to its beneficial effects through various biological activities such as chemopreventive, antitumorigenic, hepatoprotective, antioxidative and antiinflammatory effects[1].
Zomepirac-d4 sodium salt is the deuterium labeled Zomepirac sodium salt. Zomepirac sodium salt (McN-2783-21-98) is a potent prostaglandin biosynthesis inhibitor. Zomepirac sodium salt is a non-steroidal anti-inflammatory drug (NSAID). Zomepirac sodium salt can cause immune-mediated liver injury[1][2].
MF63 is a selective mPGES-1 inhibitor with an IC50 of 0.9 nM and 1.3 nM for pig mPGES-1 and human mPGES-1 enzyme, respectively. IC50 value: 0.9 nM ( pig mPGES-1); 1.3 nM (human mPGES-1)Target: mPGES-1MF63 potently inhibited the human mPGES-1 enzyme with a high degree (>1000-fold) of selectivity over other prostanoid synthases. In rodent species, MF63 strongly inhibited guinea pig mPGES-1 but not the mouse or rat enzyme. When tested in the guinea pig and a knock-in (KI) mouse expressing human mPGES-1, the compound selectively suppressed the synthesis of PGE(2), but not other prostaglandins inhibitable by nonsteroidal anti-inflammatory drugs (NSAIDs), yet retained NSAID-like efficacy at inhibiting lipopolysaccharide-induced pyresis, hyperalgesia, and iodoacetate-induced osteoarthritic pain.
PF-9184 is a potent and highly selective inhibitor of human microsomal prostaglandin E synthase-1 (mPGES-1), with an IC50 of 16.5 nM. PF-9184 inhibits IL-1β-induced PGE2 synthesis in vitro[1].
mPGES1-IN-3 (Compound 17d) is a potent and selective microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor, which exhibits excellent mPGES-1 enzyme (IC50: 8 nM), cell (A549 IC50: 16.24 nM) and human whole blood potency (IC50: 249.9 nM)[1].
Zomepirac sodium salt is a pyrrole-acetic acid structurally related to tolmetin sodium; a prostaglandin synthetase inhibitor.
Friluglanstat is a prostaglandin E synthase (mPGES-1) inhibitor, with anti-inflammatory activity[1].
Limaprost(OP1206) is a PGE1 analog and potent platelet adhesion inhibitor.Target: OthersLimaprost, an alprostadil (prostaglandin E1) analogue, is a vasodilator that increases blood flow and inhibits platelet aggregation. Limaprost is a n analog of PGE1 with structural modifications intended to give a prolonged half-life and greater potency. It is orally active in both guinea pigs and rats at doses of 100 mg/kg as an inhibitor of ADP and collagen induced platelet aggregation. It is 10-1,000 times more potent than PGE1 as a platelet adhesive inhibitor, measured in vitro. Intra-coronary injection (100 ng/kg) or intravenous injection (3 mg/kg) in anesthetized dogs causes vasodilation and increased coronary blood flow by 60-80%. Significant hypotensive effects were seen at 100 and 300 mg/kg orally in rats [1].
CAY10526 is a specific microsomal PGE2 synthase-1 (mPGES1) inhibitor. CAY10526 inhibits PGE2 production through the selective modulation of mPGES1 expression but does not affect COX-2. CAY10526 significantly suppresses tumor growth and increases apoptosis in melanoma xenografts. CAY10526 reduces BCL-2 and BCL-XL (anti-apoptotic) protein levels and increases BAX and BAK (pro-apoptotic) as well as cleaved caspase 3 levels. CAY10526 inhibits cell viability (IC50<5 μM) in three melanoma cell lines expressing mPGES1[1].
Sinensetin is a methylated flavone found in certain citrus fruits. pocess potent antiangiogenesis and anti-inflammatory, sinensetin enhances adipogenesis and lipolysis.In vitro: Sinensetin promots adipogenesis in 3T3-L1 preadipocytes growing in incomplete differentiation medium, sinensetin enhances adipogenesis and lipolysis by increasing cAMP levels. [1] Sinensetin shows anti-inflammatory activity by regulating the protein level of inhibitor κB-α (IκB-α). [2]In vivo: Sinensetin has the most potent antiangiogenesis activity and the lowest toxicity, inhibits angiogenesis by inducing cell cycle arrest in the G0/G1 phase in HUVEC culture and downregulating the mRNA expressions of angiogenesis genes flt1, kdrl, and hras in zebrafish. [3]
PGS-IN-1 is a potent inhibitor of prostaglandin synthetase (PGS) with an IC50 of 0.28 μM; also inhibits 5-lipoxygenase with an IC50 of 1.05 μM.
Vipoglanstat (BI 1029539, GS-248), a carboxamide, is a potent and selective, non-peptide and orally active small molecular inhibitor of human prostaglandin E synthase 1 (mPGES-1). Vipoglanstat (BI 1029539, GS-248) also has anti-inflammatory activity[1][2].
Suprofen-d3 (TN-762-d3) is the deuterium labeled Suprofen. Suprofen (TN-762) is a non-steroidal anti-inflammatory drug (NSAID)[1][2].
Linderaspirone A is a natural compound that can be isolated from the roots of Lindera aggregate. Linderaspirone A shows significant inhibitory effects on the production of prostaglandin E2 (PGE2),TNF-α, and IL-6 [1][2].
Bismuth Subsalicylate is the active ingredient in Pepto-Bismol and inhibits prostaglandin G/H Synthase 1/2.Target: OthersBismuth Subsalicylate reduces inflammation/irritation of stomach and intestinal lining through inhibition of prostaglandin G/H Synthase 1/2 [1]. Bismuth Subsalicylate is the active ingredient in Pepto-Bismol, an anti-diarrhea medication and antacid. In the gastrointestinal tract, Bismuth Subsalicylate is converted to salicylic acid and insoluble bismuth salts [2]. Bismuth subsalicylate treatment for 8 weeks is safe and well tolerated. This regimen appears to be efficacious for the treatment of microscopic colitis and is worthy of further study in a controlled trial [3].
HQL-79 is a potent, selective and orally active human hematopoietic prostaglandin D synthase (H-PGDS) inhibitor, highly selectively inhibits the synthesis of PGD2, and acts as an anti-allergic agent, with a Kd of 0.8 μM and an IC50 of 6 μM. Shows no obvious effect on COX-1, COX-2, m-PGES, or L-PGDS[1].
Isofezolac (LM 22070) is a non-steroidal anti-inflammatory drug (NSAID) that inhibits prostaglandin-synthetase. Isofezolac anti-inflammatory, and antipyretic properties[1][2].
YS121 is a dual inhibitor of microsomal prostaglandin E2 synthase-1 (mPGES-1; IC50=3.4 μM) and 5-lipoxygenase (5-LOX; IC50=6.5 μM). YS121 dose- dependently reduces PGE2 production with EC50=12 μM in IL-1β-stimulated A549 cells[1].
Zaloglanstat (ISC-27864) is the inhibitor of the microsomal prostaglandin E synthase-1 (mPGES-1), and can be used to study asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases, etc[1].
hPGDS-IN-1 is a hPGDS inhibitor ,with IC50 of 12 nM in the Fluorescence Polarization Assay or the EIA assay.IC50 value: 12 nMTarget: hPGDSThe detailed information please refer to WO2011044307A1 and WO2010080563A2
PF-4693627 is a potent, selective and orally bioavailable microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor (IC50=3 nM) for the treatment of inflammation caused by osteoarthritis (OA) and rheumatoid arthritis (RA)[1].
Limaprost-d3 (17α,20-dimethyl-δ2-PGE1-d3) is the deuterium labeled Limaprost. Limaprost (OP1206) is a PGE1 analogue and a potent and orally active vasodilator. Limaprost increases blood flow and inhibits platelet aggregation. Limaprost pain relief, has antianginal effects, and can be used for ischaemic symptoms research[1][2].
HPGDS inhibitor 2 is a highly potent and selective hematopoietic prostaglandin D synthase (H-PGDS) inhibitor with an IC50 of 9.9 nM[1].