protein secretion

IXA4 是一种高选择性、无毒的 IRE1 XBP1s 激活剂，通过激活 IRE1 来减少 APP 的分泌。它刺激的 IRE1 激活也增强了胰腺功能。

L-692429 (MK-0751) 是一种有效的非肽基生长激素促分泌素 (GHS) 激动剂，是一种苯并内酰胺的衍生物，可逆转糖皮质激素对 GH 分泌的抑制。L-692429 对 G 蛋白偶联受体 (G protein-coupled receptor)具有很高的亲和力，可用于研究肢端肥大症和肥胖。

LY2881835 是一种特异性 G 蛋白偶联受体 40 (GPR40) 激动剂，具有潜在的降血糖活性，可增强的葡萄糖刺激正常瘦小鼠的胰岛素分泌。LY2881835 可用于研究 2 型糖尿病。

DSS30 是一种 P25 CDK5抑制剂。DSS30通过抑制淀粉样前体蛋白裂解酶1 (BACEl) 磷酸化，减少 β-淀粉样蛋白 (Aβ) 的分泌发挥作用。DSS30 可用于预防和治疗阿尔茨海默病等神经退行性疾病。

RO-28-1675是一种直接和选择性的葡萄糖激酶 (glucokinase)激活剂，间接影响GK GKRP(glucokinase regulatory protein)复合物的活性，其效能随葡萄糖浓度升高而降低，可用于胰岛素分泌和2型糖尿病相关研究。

Glaucocalyxin A (Leukamenin F) 是来自日本黑纹病菌的一种对映型月桂基二萜，具有抗肿瘤作用。它通过调节PI3K Akt 信号通路抑制 GLI1 的核易位，诱导骨肉瘤凋亡。

RV01 是一种新型的白藜芦醇喹啉取代类似物，可抑制 DNA 损伤，降低乙醇诱导的乙醛脱氢酶 (ALDH2) 的 mRNA 表达，具有清除羟自由基的活性。RV01 降低 iNOS 的表达，具有抗神经炎症作用。RV01降低肿瘤坏死因子-a (TNF-a)和白细胞介素-6 (IL-6) mRNA 水平和分泌，抑制lps 诱导的ROS 生成和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活化，降低toll 样受体4 (TLR4)的蛋白表达，抑制lps 诱导的丝裂原活化蛋白激酶(MAPK)和核转录因子-кB (NF-кB)信号通路的激活。

TRV-120027 TFA 是一种血管紧张素 II 介导的血管收缩抑制剂，可增加心肌细胞的收缩力。它是一种偏向 β-arrestin-1 的 AT1R 激动剂，可与 ß-arrestins 结合，同时阻断 G 蛋白信号传导。 它通过阳离子通道亚家族 C3 (TRPC3) 偶联诱导急性儿茶酚胺分泌，并促进在质膜上形成由 AT1R-β-arrestin-1-TRPC3-PLCγ 组成的大分子复合物。

LHVS effectively blocks T. gondii microneme protein secretion (IC50=10 μM), gliding motility, and cell invasion. LHVS is a potent, non-selective cysteine protease inhibitor.

3-Deoxyglucosone(3-Deoxy-D-glucosone) 是美拉德反应和多元醇反应的中间体途径合成。3-Deoxyglucosone 与蛋白质氨基快速反应形成晚期糖基化末端蛋白 (AGEs)。3-Deoxyglucosone 可使谷胱甘肽过氧化物酶失活，可与低葡萄糖协同作用以增强 GLP-1 分泌，可以作为糖尿病生物学检测的标志物。

STAT3-IN-31 (compound K2071)，一种基于STATtic开发的STAT3和有丝分裂抑制剂，具备阻断有丝分裂进展及干扰纺锤体形成的功能。此外，它能够抑制胶质母细胞瘤细胞的迁移和肿瘤球体中细胞的增殖，诱导细胞衰老，并抑制抗Temozolomide的胶质母细胞瘤细胞生长，以及单核细胞趋化蛋白MCP-1的分泌，从而阻止炎症反应。

Vasopressin-d5 TFA为Vasopressin-d5的TFA盐形式，并作为Vasopressin的同位素标记物。Vasopressin本身是一种在下丘脑中部合成的环状九肽。它参与下丘脑-垂体-肾上腺轴中的功能，通过加强对促皮质素释放因子的刺激，从而调控垂体的促皮质素分泌。此外，Vasopressin还能作为神经递质，通过与特定的G蛋白偶联受体相结合来发挥作用。

M351-0056 是一种免疫检查点蛋白VISTA的激动剂，可以降低VISTA诱导的细胞因子分泌，促进VISTA介导的T细胞增殖，并具有免疫调节作用。M351-0056 能在小鼠模型中改善Imiquimod引发的银屑病性皮炎。

AS1269574 是口服有效的GPR119激动剂，在表达人 GPR119 的 HEK293 细胞中EC50为 2.5 μM。它激活 TRPA1 阳离子通道，刺激胰高血糖素样肽-1分泌。它仅在高糖条件下特异性诱导胰腺 β 细胞分泌葡萄糖依赖性胰岛素。它在 2 型糖尿病的研究中具有价值。

BMS-986118 is a full agonist of GPR40, is a G-protein-coupled receptor expressed primarily in pancreatic islets and intestinal L-cells that has been a target of significant recent therapeutic interest for type II diabetes. Activation of GPR40 by partial a

AG 85 is a major secretion protein of Mycobacterium tuberculosis.

Neuropeptide Y (NPY) (3-36) is a C-terminal fragment of NPY, a neuropeptide involved in controlling appetite, blood pressure, cardiac contractility, and intestinal secretion. NPY (3-36) is an endogenous peptide produced by cleavage of NPY by dipeptidyl peptidase 4 (DPP-4). It binds selectively to the NPY receptor Y2 (Ki = 0.41 nM in CHP 234 cells) over the Y1 receptor, where it does not bind at concentrations up to 1 μM. NPY (3-36) (0.1 nM) increases migration of human umbilical vein endothelial cells (HUVECs) by 80% after 12 hours in an in vitro wound closure assay. NPY (3-36) corresponds to residues 3-36 of the human and rat protein sequence.

Osteocalcin (1-49) is a non-collagenous peptide that is secreted by osteoblasts and odontoblasts and comprises 1-2% of the total protein in bone. Secretion of osteocalcin (1-49) is stimulated by 1,25-dihydroxy vitamin D and plasma levels increase in diseases that induce dysregulated bone turnover such as osteoporosis, Paget's disease, and primary hyperparathyroidism. Osteocalcin (1-49) is positively correlated with insulin sensitivity and negatively correlated with high blood glucose levels in women. In vitro, osteocalcin induces chemotaxis of MDA-MB-231 breast cancer cells, human peripheral blood monocytes, and rat osteosarcoma cells with osteoblast-like characteristics. It is also expressed by vascular smooth muscle cells (VSMCs) displaying an osteoblast-like phenotype and has been positively associated with calcification of aortic tissue and heart valves in humans.

Kisspeptin-54 is a peptide ligand of the orphan G protein-coupled receptor GPR54 (Kis = 1.81 and 1.45 nM for rat and human receptors, respectively).1 It is a 54 amino acid peptide encoded by the metastasis suppressor gene KISS-1. Kisspeptin-54 induces calcium mobilization in CHO-K1 cells expressing rat and human receptors (EC50s = 1.39 and 5.47 nM, respectively). It also induces arachidonic acid release in CHO cells expressing rat and human GPR54 in a concentration-dependent manner. Kisspeptin-54 (10-1,000 nM) inhibits insulin secretion from isolated mouse pancreatic β-cells in the presence of 2.8 mM, but not 11.1 mM, glucose.2 Kisspeptin-54 (1-5 nmol, i.c.v.) increases serum levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH) in mice, an effect which is reversed by the gonadotropin releasing hormone (GNRH) antagonist acycline.3References1. Kotani, M., Detheux, M., Vandenbogaerde, A.L., et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem. 276(37), 34631-34636 (2001).2. Vikman, J., and Ahrén, B. Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets. Diabetes Obes. Metab. 11(Suppl 4), 197-201 (2009).3. Gottsch, M.L., Cunningham, M.J., Smith, J.T., et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145(9), 4073-4077 (2004). Kisspeptin-54 is a peptide ligand of the orphan G protein-coupled receptor GPR54 (Kis = 1.81 and 1.45 nM for rat and human receptors, respectively).1 It is a 54 amino acid peptide encoded by the metastasis suppressor gene KISS-1. Kisspeptin-54 induces calcium mobilization in CHO-K1 cells expressing rat and human receptors (EC50s = 1.39 and 5.47 nM, respectively). It also induces arachidonic acid release in CHO cells expressing rat and human GPR54 in a concentration-dependent manner. Kisspeptin-54 (10-1,000 nM) inhibits insulin secretion from isolated mouse pancreatic β-cells in the presence of 2.8 mM, but not 11.1 mM, glucose.2 Kisspeptin-54 (1-5 nmol, i.c.v.) increases serum levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH) in mice, an effect which is reversed by the gonadotropin releasing hormone (GNRH) antagonist acycline.3 References1. Kotani, M., Detheux, M., Vandenbogaerde, A.L., et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem. 276(37), 34631-34636 (2001).2. Vikman, J., and Ahrén, B. Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets. Diabetes Obes. Metab. 11(Suppl 4), 197-201 (2009).3. Gottsch, M.L., Cunningham, M.J., Smith, J.T., et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145(9), 4073-4077 (2004).

3-Iodothyronamine is derived from the deiodination and decarboxylation of endogenous thyroxine. It activates the G protein-coupled receptor known as trace amine-associated receptor 1 at nanomolar concentrations whereupon it rapidly influences thyroid hormone actions including body temperature, heart rate, and cardiac output. It has also been reported to function in controlling lipid and glucose utilization, hormonal secretion, and neuronal function, and has been considered for use in chemically-induced hibernation for medical purposes.

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

12(S)-HETrE是一种内源性代谢物，由血小板中的12-脂氧合酶（12-LOX）氧化ω-6 PUFA dihomo-γ-linolenic acid(DGLA)产生，作用于Gαs偶联的G蛋白偶联受体，具有抗血栓形成的作用，在心血管疾病具有潜在的治疗作用。12(S)-HETrE 在体外可抑制激动剂介导的血小板活化（IC50 = 40 μM）、α 颗粒分泌、整合素 αⅡbβ3 活化、Rap1 活化和凝血酶诱导的血块回缩。

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

cis-9,10-Methyleneoctadecanoic acid is a cyclopropane fatty acid that has been found in bacteria and the digestive gland of P. globosa. It is a component of S. aureus cell membranes and levels decrease upon treatment with carvacrol. cis-9,10-Methyleneoctadecanoic acid is secreted by H. pylori and enhances histamine- and dibutyryl cAMP-stimulated acid secretion in isolated guinea pig parietal cells. It also activates protein kinase C (PKC) in a calcium-dependent manner.