human whole blood

CJ-42794 (CJ-042794) is a selective antagonist of the prostaglandin E receptor subtype 4 (EP4), inhibiting [3H]-PGE2 binding to the human EP4 receptor with a mean pKi of 8.5. It exhibits a binding affinity that is at least 200-fold more selective for the human EP4 receptor than for other human EP receptor subtypes (EP1, EP2, and EP3) (IC50: 8.5 (pKi)).

Cot inhibitor-1 is a selective inhibitor of Cot protein kinase (also known as Tpl2 or MAP3K8) (IC50 at 28 nM). Cot inhibitor-1 inhibited TNF-alpha production in human whole blood with IC50 of 5.7 nM. Cot is involved in a variety of cellular signaling pathways, particularly those involved in inflammation and immune responses. Cot inactivate-1 inhibits Cot activity and may have potential therapeutic effects on rheumatoid arthritis, inflammatory bowel disease and some types of cancer.

Cot inhibitor-1 hydrochloride is an inhibitor of tumor progression loci-2 kinase (IC50 = 28 nM) and inhibits the production of TNF-α in human whole blood (IC50 = 5.7 nM).

Cot inhibitor-2 is a cot (Tpl2 MAP3K8) inhibitor (IC50: 1.6 nM) with potency, selectivity and oral activity. cot inhibitor-2 inhibits LPS-stimulated TNF-α production in human whole blood with an IC50 of 0.3 μM.

LM-1685 is a potent and selective inhibitor of COX-2 IN human monocytes and whole blood with IC50 of 0.65µM and IC50 = 4.3μM, respectively, and is a potential compound for the treatment of inflammation.

Tebufelone is a potent in vitro inhibitor of CO , a novel non-steroidal anti-inflammatory drug (NSAID) belonging to the di-tert-butylphenol (DTBP) class that has shown potent anti-inflammatory, analgesic and anti-reticulitis properties in various animal models. Tebufelone potently inhibits the formation of prostaglandins (PGE2) and blocks the formation of lipoxygenase pathway products [leukotriene (LTB4)] in rat macrophages (IC50 = 20 microM) and human whole blood (IC50 = 22 microM) in vitro. = 20 microM) and human whole blood (IC50 = 22 microM) from the formation of lipoxygenase pathway products [leukotriene (LTB4)] in vitro.

Loxoprofen (Koloxo) is an anti-inflammatory non-steroidal medicine.

Etoricoxib (MK-663) is a synthetic, nonsteroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and potential antineoplastic properties. Etoricoxib specifically binds to and inhibits the enzyme cyclooxygenase-2 (COX-2), resulting in inhibition of the conversion of arachidonic acid into prostaglandins. Inhibition of COX-2 may induce apoptosis and inhibit tumor cell proliferation and angiogenesis.

PF-8380 is an effective and orally available autotaxin inhibitor (IC50: 2.8 nM, in isolated enzyme assay; 101 nM, in the human whole blood). It modulates lysophosphatidic acid (LPA) levels in vivo vitro by directly inhibiting autotaxin; reduces LPA levels both in plasma and at the site of inflammation.

(S)-BI 665915 is an orally active inhibitor of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) with an IC50 of 1.7 nM for FLAP binding.

AZD2906, a selective glucocorticoid receptor (GR) agonist, demonstrates inhibitory concentrations (IC50s) of 2.2 nM in human GR, 0.3 nM in rat peripheral blood mononuclear cells (PBMC), 41.6 nM in human whole blood, and 7.5 nM in rat whole blood, respectively[1]. Additionally, it induces an increase in micronucleated immature erythrocytes within rat bone marrow.

AZD7624 is an p38 inhibitor. It has potent anti-inflammatory activity.

PF-03715455 potently inhibits LPS-induced TNFα production in human whole blood (IC50=1.7 nM). PF-03715455 is an effective inhibitor of inhaled p38 MAPK. PF-03715455 displays some selectivity for p38α over p38β (respective IC50: 0.88 and 23 nM). PF-0371545

AGU654 (Compound 44) is a selective mPGES-1 inhibitor with an IC50 value of 2.9 nM against mPGES-1. By inhibiting mPGES-1, AGU654 interrupts the pathway where COX-1 2 converts arachidonic acid to prostaglandin E2 (PGE2), effectively reducing inflammatory responses, pain, and fever symptoms. In models using activated human monocyte-derived macrophages and whole blood, AGU654 selectively inhibits PGE2 production induced by bacterial endotoxins, while preserving the production of other prostaglandins. In guinea pig models, AGU654 significantly alleviates fever, inflammation, and inflammatory pain, demonstrating excellent anti-inflammatory, analgesic, and antipyretic effects. AGU654 holds promise as a new approach for researching inflammatory diseases and pain.

STAT3-IN-37 (Compound 101) is an inhibitor of STAT3, with an IC50 of 15 nM as measured by DNA-HTRF assay and 2 nM as determined through human whole blood SOCS3 qPCR assay.

NLRP3-IN-60 (Compound 39) is an orally bioavailable inhibitor of NLRP3. It effectively suppresses pyroptosis in THP-1 cells with an IC50 of 13 nM and inhibits IL-1β release in human whole blood, exhibiting an IC50 of 225 nM.

Phe-Pro-Arg-PABA-Resorufin is a Chromogenic and fluorogenic peptide substrate for the highly sensitive detection of proteases in biological matrices. The substrate is also applicable to the sensitive detection of the thrombin inhibitor dabigatran in human

Tpl2 kinase inhibitor is an inhibitor of tumor progression locus 2 (Tpl2; IC50= 0.05 μM).1It is selective for Tpl2 over MEK, p38 MAPK, Src, MK2, and PKC (IC50s = >40, 180, >400, 110, and >400 μM, respectively). Tpl2 kinase inhibitor inhibits LPS-induced TNF-α production in isolated human monocytes and whole blood (IC50s = 0.7 and 8.5 μM, respectively). It enhances differentiation induced by calcitriol in HL-60 and U937 leukemia cells when used at a concentration of 5 μM.2Tpl2 kinase inhibitor (5 μM) inhibits the proliferation of KG-1a leukemia cells.3 1.Garvin, L.K., Green, N., Hu, Y., et al.Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationshipsBioor. Med. Chem. Lett.15(23)5288-5292(2005) 2.Wang, X., and Studzinski, G.P.Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cellsJ. Steroid. Biochem. Mol. Biol.121(1-2)395-398(2010) 3.Wang, X., Gocek, E., Novik, V., et al.Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D3Cell Cycle9(22)4542-4551(2010)

4-hydroxy Valsartan is a major metabolite of the angiotensin II type 1 (AT1) receptor antagonist valsartan . It reduces platelet aggregation induced by epinephrine and collagen but not ADP in human whole blood.

T-5342126 is a toll-like receptor 4 (TLR4) antagonist that reduces LPS-induced production of nitric oxide (NO) in RAW 264.7 cells (IC50 = 27.8 μM) and decreases LPS-induced IL-8, TNF-α, and IL-6 production in isolated human whole blood (IC50s = 110.5, 315.6, and 318.4 μM, respectively). T-5342126 (82 mg kg) also reduces ethanol intake and the abundance of ionized calcium-binding adapter molecule 1 (Iba1), a marker of microglial activation, in the central nucleus of the amygdala in ethanol-dependent mice.

17(S)-HDHA is a primary mono-oxygenation product of docosahexaenoic acid in human whole blood, human leukocytes, and mouse brain. 17(S)-HDHA serves as a precursor to 17(S)-resolvins and has intrinsic biological activity, such as the inhibition of TNF-α-induced interleukin-1β expression in human glioma cells and inhibition of TNF-α-induced leukocyte trafficking to the mouse air pouch.

8-iso Prostaglandin F2β (8-iso PGF2β) is an isomer of PGF2α of non-enzymatic origin. It is one of 64 possible isomers of PGF2α which can be produced by free radical peroxidation of arachidonic acid. 8-iso PGF2β exhibits very weak contraction of human umbilical vein artery and does not promote aggregation of human whole blood. However, 8-iso PGF2β moderately contracts both the canine and porcine pulmonary vein, although the effect is much weaker than that exhibited by other isoprostanes such as 8-iso PGE1, 8-iso PGE2, or 8-iso PGF2α. 8-iso-15-keto PGF2β is a potential metabolite of 8-iso PGF2β via the 15-hydroxy PG dehydrogenase pathway. There are no published reports on the formation or biological activity of 8-iso-15-keto PGF2β.

CXCR2-IN-2 is a selective CXCR2 antagonist that is brain penetrant and orally bioavailable, with IC50 values of 5.2 nM and 1 nM in the β-arrestin assay and CXCR2 Tango assay, respectively. It exhibits approximately 730-fold selectivity over CXCR1 and greater than 1900-fold selectivity over all other chemokine receptors. Furthermore, CXCR2-IN-2 effectively inhibits Gro-α induced CD11b expression in human whole blood, displaying an IC50 of 0.04 μM[1].

Potent and selective cytosolic phospholipase A2 alpha (cPLA2α) inhibitor (IC50 = 20 nM). Selective for cPLA2α over secreted PLA2α (sPLA2α; exhibits no inhibition at 10 μM). Inhibits cPLA2α-dependent inflammatory responses in vitro in guinea pig and human whole-blood assays. Improves diet-induced liver injury and CCl4-induced hepatic fibrosis in vivo. Orally bioavailable.