platelet production

Anagrelide (Xagrid) 是III 型磷酸二酯酶(PDEIII)抑制剂 (IC50=36 nM)，是咪唑喹唑啉衍生物。它能够抑制血小板生成，以及抗血栓形成作用，可用作血小板聚集抑制剂。

BIRM 271 是一种新型花生四烯酸释放抑制剂，可阻断白三烯B4和人中性粒细胞中的血小板活化因子生物合成。BIRM 271 和 BIRM 270 属于对映异构体，对白三烯B4 的产生有抑制作用，IC50 为40 nM。

Pentoxifylline (PTX) 是一种具有口服活性的磷酸二酯酶非选择性抑制剂，具有免疫调节、抗炎、抗纤溶、抗增殖和血液流变学改善作用。它可研究周围血管疾病、脑血管疾病和其他一些涉及局部微循环缺陷的疾病。

Cepharanthine (NSC-623442) 属于天然生物碱，可抑制 TNF-α 介导的 NFκB 刺激、质膜脂质过氧化和血小板聚集，并抑制细胞因子的产生。Cepharanthine 具有抗炎、抗氧化、抗肿瘤活性。

Eltrombopag Olamine (Eltrombopag diethanolamine salt) 是 Eltrombopag 的口服活性乙醇胺盐，是一种血小板生成素(TPO)受体激动剂，用于血小板减少的某些病症研究。

p-Hydroxycinnamic acid (NSC-59260) 是常见的食用酚，可抑制血小板活性，对血栓素 B2 和前列腺素 E2 的 IC50值分别为 371 和 126 μM。

Avatrombopag (YM477) 是一种新型口服血小板生成素 (TPO) 受体激动剂，可激活 TPO 受体并增加巨核细胞增殖 分化和血小板生成。

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 EC 50 of 3.3 nM. It effectively mimics the biological activities of TPO, stimulating platelet production by activating the intracellular signaling system and facilitating the generation of platelets and megakaryocytes from hemopoietic precursor cells. Additionally, Avatrombopag hydrochloride serves as a substrate for cytochrome P450 (CYP) 2C9 and CYP3A.

AG126 (Tyrphostin AG126) 是一种酪氨酸激酶抑制剂，可阻止丝裂原活化蛋白激酶 p42MAPK(ERK2) 的激活。

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，一种Eltrombopag衍生物，为促血小板生成素(Tpo)受体激动剂，旨在促进血小板生成，用于研究特定类型的血小板减少症。

2-Chloroadenosine-5'-O-diphosphate是一种腺苷5'二磷酸（ADP）的衍生物。它在浓度依赖性的方式下，促进了人类富含血小板的血浆中的聚集，并抑制了由前列腺素E2（PGE2）诱导的环磷酸腺苷（cAMP）的产生。2-Chloroadenosine-5'-O-diphosphate引起预收缩的孤立的豚鼠taenia coli条带放松（pD2 = 6.74），降低大鼠的动脉血压。此外，它还抑制了热休克蛋白70（Hsp70）家族成员mortalin的ATP酶活性（人类酶的表观Ki = 45.05 µM）。

Rp-Adenosine-5'-O-(1-thiotriphosphate)（Rp-ATP-α-S）是一种含硫核苷酸衍生物ATP-α-S的异构体，同时也是嘌呤P2Y1受体的激动剂。在表达人类P2Y1受体的HEK293细胞中，Rp-ATP-α-S能增加钙的动员（EC50 = 75 nM）。该化合物与洗涤的人类孤立血小板结合（Ki = 156 nM），抑制由ADP引发的人类富血小板血浆（PRP）的聚集（pA2 = 4.74），并且能够抑制前列腺素E1（PGE1）在人类孤立PRP中引发的cAMP产生（pA2 = 5.26）。同时，Rp-ATP-α-S还能引起用氨基甲酰胆碱预先缩紧的豚鼠结肠条带的松弛（EC50 = 56 nM）。此外，Rp-ATP-α-S已经被用于合成被细菌核糖开关识别的环状二核苷酸。

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为一种TPO (thrombopoietin protein)的Fc肽融合蛋白模拟物，属于肽体分子(peptide-body)类。该化合物通过激活血小板生成素受体 (TPO receptor)，有效促进血小板的产生。