platelet production

BIRM 271 is a novel arachidonic acid release inhibitor that blocks leukotriene B4 and platelet-activating factor biosynthesis in human neutrophils. BIRM 271 and BIRM 270 are enantiomers that inhibit the production of leukotriene B4 with IC50 of 40 nM.

Pentoxifylline (PTX) modulates immunologic activity by stimulating cytokine production. Pentoxifylline is a methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It also inhibits platelet aggregation and improves blood flow by increasing erythrocyte and leukocyte flexibility.

Cepharanthine (NSC-623442) is a natural alkaloid that inhibits TNF-α-mediated NFκB stimulation, plasma membrane lipid peroxidation, and platelet aggregation, as well as cytokine production. Cepharanthine exhibits anti-inflammatory, antioxidant, and antitumor activities.

Eltrombopag Olamine (Eltrombopag diethanolamine salt) is an orally active small-molecule, nonpeptide thrombopoietin receptor agonist that stimulates megakaryopoiesis. It binds to and activates the transmembrane domain of the platelet thrombopoietin receptor (TPO-R or CD110), promoting the proliferation and differentiation of megakaryocytic cells and enhancing platelet production.

p-Hydroxycinnamic acid (NSC-59260) can inhibit platelet activity, with IC50s of 371 μM, 126 μM for thromboxane B2 production and lipopolysaccharide-induced prostaglandin E2 generation, respectively.

Avatrombopag (YM477) is a new oral thrombopoietin (TPO) receptor agonist, activating TPO receptor and increasing megakaryocytic proliferation differentiation and platelet production.

AG126 (Tyrphostin AG126) selectively inhibits the phosphorylation of ERK1 (p44) and ERK2 (p42) at 25-50 μM. It blocks the production of TNF-α in vitro2 and in vivo, attenuating signaling through NF-κB, the induced expression of COX-2 and iNOS, and the inflammatory response in diverse animal models. AG-126 weakly inhibits epidermal GFRK (IC50: 450 μM) and platelet-derived GFRK (IC50 > 100 μM).

Anagrelide (Xagrid) is a Platelet-reducing Agent. The mechanism of action of anagrelide is as a Phosphodiesterase 3 Inhibitor. The physiologic effect of anagrelide is by means of Decreased Platelet Production.

Gea 3162 is a potent inhibitor of ADP-induced platelet aggregation in platelet rich plasma (PRP). GEA 3162 stimulates cGMP production in granulocytes, platelets, and polymorphonuclear leukocytes.

Ono 6240 is an antagonist of platelet-activating factor. Ono 6240 prevents airway eosinophilia by inhibiting production of IL-2 and IL-5.

2-chloro Palmitic acid is a monochlorinated form of palmitic acid . It is produced in a myeloperoxidase (MPO) and time-dependent manner in neutrophils stimulated by phorbol 12-myristate 13-acetate . 2-chloro Palmitic acid (10 μM) induces neutrophil extracellular trap (NET) formation (NETosis) in human neutrophils, increasing DNA release from neutrophils, colocalization of MPO with extracellular DNA (ecDNA), and trapping of E. coli. It increases COX-2 protein levels in human coronary artery endothelial cells (HCAECs) when used at a concentration of 50 μM and increases production of P-selectin, von Willebrand factor, and angiopoietin-2 in HCAECs, as well as neutrophil and platelet adherence, when used at a concentration of 10 μM. 2-chloro Palmitic acid (10-50 μM) also induces apoptosis in THP-1 cells and primary human monocytes and increases caspase-3 activity in THP-1 cells.

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA2α with an IC50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE2 and LTC4 in cells (IC50 = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA2s with more than a hundred-fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells, interleukin-1-induced PGE2 synthesis in mesangial cells, and the production of PGE2, LTs, and platelet-activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.

1,2,3-Trieicosapentaenoyl-rac-glycerol (EPA-TG) is a glycerol ester of eicosapentaenoic acid , which is an ω-3 fatty acid. An EPA-TG emulsion, administered i.v., lowers leukotriene B4 production by 40% in polymorphonuclear leukocytes from rabbits and reduces platelet aggregation. It suppresses natural killer cell activity both in vitro and in vivo, in human lymphocytes and murine spleens, respectively, with the in vivo effects lasting up to seven days.

Prostaglandin D2 (PGD2) plays a pharmacological role in allergic and asthmatic anaphylaxis, normal physiological sleep and lowering of body temperature, as well as inhibits platelet aggregation and relaxes vascular smooth muscle. PGDM is a major urinary metabolite of PGD2 with a unique lower sidechain that readily undergoes reversible cyclization. It is used as a biomarker to assess endogenous production of PGD2.

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

β-Chamigrenal has anti-inflammatory activity, it has inhibitory effects on lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in RAW 264.7 macrophages. Chamigrenal shows platelet-activating factor antagonistic activity and the IC(50)

Avatrombopag hydrochloride (AKR-501) is an orally active, nonpeptide agonist of the thrombopoietin (TPO) receptor with an EC50 of 3.3 nM. It effectively mimics TPO by stimulating platelet production through activation of the intracellular signaling system, facilitating platelet and megakaryocyte generation from hemopoietic precursor cells. Additionally, Avatrombopag hydrochloride serves as a substrate for cytochrome P450 [CYP] 2C9 and CYP3A.

Orlistat-d3 is intended for use as an internal standard for the quantification of orlistat by GC- or LC-MS. Orlistat is a digestive lipase inhibitor. It inhibits diacylglycerol lipase α (DAGLα), DAGLβ, α β-hydrolase domain-containing protein 12 (ABHD12), ABHD16A, and platelet-activating factor acetylhydrolase (PAF-AH; IC50s = 0.06, 0.1, 0.08, 0.03, and 0.05 µM, respectively), as well as pancreatic lipase and hormone-sensitive lipase (IC50s = 0.65 and 2.1 µg ml, respectively) but does not inhibit fatty acid amide hydrolase (FAAH) or KIAA1363 (IC50s = >100 µM for both). Orlistat decreases ionomycin-induced production of the endocannabinoid 2-arachidonoyl glycerol (2-AG) in N18TG2 murine neuroblastoma cells when used at a concentration of 1 µM. It also inhibits fatty acid synthase (FASN; Kiapp = ~0.1 µM for the human enzyme) and the proliferation of PC3 prostate cancer cells in a concentration-dependent manner. Orlistat (10 mg kg) decreases serum cholesterol levels and total bod......

Eltrombopag Methyl Ester, a derivative of Eltrombopag, functions as a thrombopoietin (Tpo) receptor agonist to enhance platelet production and is employed in the study of certain thrombocytopenia variants.

2-Chloroadenosine-5'-O-diphosphate, a purine nucleotide adenosine 5'diphosphate (ADP) derivative, demonstrates multiple biological activities. It promotes aggregation and inhibits cyclic AMP (cAMP) production, triggered by prostaglandin E2 (PGE2), in a concentration-dependent manner within isolated human platelet-rich plasma. Additionally, this compound facilitates the relaxation of precontracted isolated guinea pig taenia coli strips (pD2 = 6.74) and reduces arterial blood pressure in rats. Moreover, 2-Chloroadenosine-5'-O-diphosphate significantly inhibits the ATPase activity of mortalin, a member of the heat shock protein 70 (Hsp70) family, with an apparent Ki of 45.05 µM for the human enzyme.

Rp-Adenosine-5'-O-(1-thiotriphosphate) (Rp-ATP-α-S), a sulfur-containing nucleotide derivative isomer and a purinergic P2Y1 receptor agonist, promotes calcium mobilization in HEK293 cells expressing the human P2Y1 receptor (EC50 = 75 nM). This compound exhibits binding affinity to washed isolated human platelets (Ki = 156 nM) and attenuates ADP-induced aggregation in human platelet-rich plasma (PRP; pA2 = 4.74), as well as inhibits cAMP production triggered by prostaglandin E1 (PGE1) in human PRP (pA2 = 5.26). Furthermore, it triggers relaxation in carbamoylcholine-constricted guinea pig taenia coli strips (EC50 = 56 nM). Rp-ATP-α-S also contributes to the synthesis of cyclic dinucleotides, recognized by bacterial riboswitches.

U-51605, a stable analog of the endoperoxide prostaglandin H2 (PGH2), functions as an inhibitor with greater selectivity towards prostacyclin (PGI) synthase over thromboxane (TX) synthase. It also acts as a partial agonist at TP receptors. Studies show that at a concentration of 2.8 µM, U-51605 effectively inhibits PGI synthase in human foreskin fibroblasts, while a concentration of 5.6 µM is required to inhibit human platelet TX synthase. Furthermore, U-51605, at up to 1 µM, decreases the release of prostacyclin in SHR aorta triggered by the calcium ionophore A-23187 without impacting TXA2 production, and notably enhances the release of PGE2 and PGF2α.

(±)17(18)-EpETE-Ethanolamide, an ω-3 endocannabinoid epoxide, originates from eicosapentaenoic ethanolamide (EPEA) through cytochrome P450 (CYP) epoxygenases action and is decomposed by soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FA, AH). Its endogenous synthesis occurs in LPS-stimulated and EPEA-supplemented BV-2 microglia cells, a process inhibited by the CYP inhibitor ketoconazole. This compound mitigates IL-6 and nitrite levels while enhancing IL-10 production following LPS exposure in BV-2 microglia. At a dose of 50 µM, it prevents platelet aggregation caused by arachidonic acid but not that triggered by ADP, collagen, or ristocetin. Additionally, it facilitates the dilation of constricted bovine coronary arteries (ED50= 1.1 µM) and blocks VEGF-driven tubulogenesis in human microvascular endothelial cells (HMVECs).

Romiplostim is a peptide-body (peptide-body) molecule and an Fc peptide fusion protein analog of TPO (thrombopoietin protein). It functions by activating the thrombopoietin receptor (TPO receptor) to increase platelet production.