ng 3

Terevalefim 是干细胞生长因子的一种类似物，对c-Met 受体有选择性激活作用。

PD 404182 是一种人类二甲基精氨酸二甲基氨基水解酶 1 (DDAH1) 抑制剂，具有抗血管生成和抗病毒活性，可用于研究心血管疾病和病毒感染。

KUNG38 is a purine-based inhibitor of Grp94.

TNG348 是一种口服活性的去泛素化酶USP1抑制剂，用于研究 BRCA1 2 突变或 HRD+ 型癌症。

Romidepsin (FR 901228) 是一种 HDAC 抑制剂，抑制 HDAC1 2 4 6 (IC50=36 47 510 1400 nM)。Romidepsin 具有抗肿瘤活性，可以用于治疗外周 T 细胞淋巴瘤和皮肤 T 细胞淋巴瘤。

Dxd (OQM5SD32BQ) 是一种有效的DNA 拓扑异构酶 I 抑制剂，IC50值为 0.31 μM，用作HER2靶向ADC 的偶联药物。

Datopotamab deruxtecan (DS-1062) 是一种滋养层细胞表面抗原 2 (TROP2) 靶向抗体药物偶联物 （ADC），具有抗肿瘤活性。Datopotamab deruxtecan 在外周血淋巴细胞存在下诱导显着的抗体依赖性细胞毒性，可在异种移植模型中抑制肿瘤生长。

Purvalanol B (NG 95) 是选择性可逆的 ATP 竞争性 CDK 抑制剂。它在一系列其他蛋白激酶 (IC50>1000 nM) 中显示出对 CDK 的选择性。它抑制耐氯喹菌株 P. falciparum 的生长。

KRN7000 analog 3（Compound 14），这种α-GalCer类似物具有4-苯氧基替代基，是一种高效的iNKT激动剂。在mNK1.2细胞中，KRN7000 analog 3诱导的IL-2细胞因子分泌水平（49.2-62.6 ng mL）显著高于α-GalCer（44.1 ng mL）。因此，KRN7000 analog 3在抗肿瘤药物和疫苗佐剂的开发中具有潜在的应用价值。

BIO5192 hydrate is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd<10 pM). BIO5192 hydrate selectively binds to α4β1 (IC50=1.8 nM) over a range of other integrins. BIO5192 hydrate results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels[1][2]. The combination of BIO5192 hydrate (1 mg kg; i.v.) and Plerixafor (5 mg kg; s.c.) exert an additive effect on progenitor mobilization[1].BIO5192 hydrate (30 mg kg; s.c; bid; during days 5 through 14) delays paralysis associated with EAE (experimental autoimmune encephalomyelitis)[2].BIO5192 hydrate (1 mg kg, i.v.) shows the terminal half-life is 1.1 hours. BIO5192 hydrate (3, 10, and 30 mg kg; s.c.) shows half-lives of 1.7, 2.7, and 4.7 hours, respectively. The blood plasma curves show that the AUC for the s.c. route of administration increased about 2.5-fold from 5,460 h*ng ml for the 3 mg kg dose to 14,175 h*ng ml for the 30 mg kg[1]. Animal Model: C57BL 6J x 129Sv J F1 mice[1] [1]. Ramirez P, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009;114(7):1340‐1343. [2]. Leone DR, et al. An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther. 2003;305(3):1150-1162.

Certolizumab pegol (Certolizumab) 是一种聚乙二醇化和人源化抗 TNF-α 单克隆抗体，可用于研究类风湿性关节炎 （RA）、银屑病关节炎 （PsA） 和中轴型脊柱关节炎 （axSpA）等自身免疫疾病。

Maresin conjugates in tissue regeneration 3 (MCTR3) is a specialized pro-resolving mediator (SPM) synthesized from docosahexaenoic acid in macrophages. DHA is oxidized to maresin 1 , which is converted to MCTR1 by glutathione S-transferase Mu 4 or leukotriene C4 synthase, then to MCTR2 by γ-glutamyl transferase, and to MCTR3 by dipeptidase. MCTR3 accelerates tissue regeneration in planaria (1 and 100 nM) approximately as potently as MCTR2 and more potently than MCTR1. Pretreatment with MCTR3 prior to E. coli administration in mice reduces neutrophil infiltration, shortens the inflammatory resolution period, and increases phagocytosis of E. coli by macrophages. When administered at a dose of 100 ng 12h post E. coli infection in a mouse model of peritonitis, MCTR3 selectively reduces the amount of the eicosanoids PGD2 , PGE2 , PGF2α , and TXB2 in the exudate.

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)

β-Defensin-3 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It inhibits the growth of the periodontopathogenic and cariogenic bacteria F. nucleatum, S. mutans, S. sobrinus, S. salivarius, and L. casei (MICs = 12.5-100 mg/l). It also inhibits the growth of S. aureus, S. pyogenes, P. aeruginosa, E. coli, and C. albicans. β-Defensin-3 stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes when used at a concentration of 30 μg/ml. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 5, and 20 μg/ml, respectively. β-Defensin-3 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose.

Gliovirin is a fungal metabolite that has been found inT. harzianumand has fungicidal, antimicrobial and anti-inflammatory activities.1It is active against the plant pathogenic fungusP. ultimum(MIC = 60 ng/ml) and the parasiteT. brucei brucei(IC50= 90 ng/ml), but has no effect on the plant pathogenic fungiR. solani,P. omnivorum,T. basicola,R. arrhizus, andV. dahliaeor the bacteriaB. thuringiensis,P. fluorescens, andX. malvacearumwhen used at concentrations up to 1,000 ng/ml.2,3Gliovirin decreases phorbol 12-myristate 13-acetate (TPA)- and ionomycin-induced increased expression of COX-2 (IC50= 1 μM) and protein levels of IL-2 in Jurkat cells (IC50= 5.2 μM).1 1.Rether, J., Serwe, A., Anke, T., et al.Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirinBiol. Chem.388(6)627-637(2007) 2.Howell, C.R., and Stipanovic, R.D.Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimumCan. J. Microbiol.29(3)321-324(1983) 3.Iwatsuki, M., Otoguro, K., Ishiyama, A., et al.In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationshipsJ. Antibiot. (Tokyo)63(10)619-622(2010)

β-Defensin-2 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.1It inhibits the growth of periodontopathogenic and cariogenic bacteria, includingP. gingivalisandS. salivarius.2β-Defensin-2 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes.3It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-2 induces IL-31 production by human peripheral blood-derived mast cellsin vitrowhen used at a concentration of 10 μg/ml and by rat mast cellsin vivofollowing a 500 ng intradermal dose.4Expression of β-defensin-2 is increased in psoriatic skin and chronic wounds.5,6 1.Lehrer, R.I.Primate defensinsNat. Rev. Microbiol.2(9)727-738(2004) 2.Ouhara, K., Komatsuzawa, H., Yamada, S., et al.Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cellsJ. Antimicrob. Chemother.55(6)888-896(2005) 3.Niyonsaba, F., Ushio, H., Nakano, N., et al.Antimicrobial peptides human β-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokinesJ. Invest. Dermatol.127(3)594-604(2007) 4.Niyonsaba, F., Ushio, H., Hara, M., et al.Antimicrobial peptides human β-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cellsJ. Immunol.184(7)3526-3534(2010) 5.Huh, W.-K., Oono, T., Shirafuji, Y., et al.Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skinJ. Mol. Med. (Berl.)80(10)678-684(2002) 6.Butmarc, J., Yufit, T., Carson, P., et al.Human β-defensin-2 expression is increased in chronic woundsWound Repair Regen.12(4)439-443(2004)

13C15-Nivalenol is intended for use as an internal standard for the quantification of nivalenol by GC- or LC-MS. Nivalenol is a trichothecene mycotoxin that has been found inFusarium.1It is lethal to mice (LD50= 6.9 mg kg).2Nivalenol (5, 10, and 15 mg kg) also induces thymic, splenic, and Peyer's patch cell apoptosis in mice.3 1.Yang, Z., Concannon, J., Ng, K.S., et al.Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulationSci. Rep.630263(2016) 2.Yoshizawa, T., and Morooka, N.Studies on the toxic substances in the infected cereals (part 3): Acute toxicities of new trichothecene mycotoxins: Deoxynivalenol and its monoacetateJ. Food Hyg.15(4)261-269(1974) 3.Poapolathep, A., Ohtsuka, R., Kiatipattanasakul, W., et al.Nivalenol-induced apoptosis in thymus, spleen and Peyer's patches of miceExp. Toxicol. Pathol.53(6)441-446(2002)

Atrazine-3-mercaptopropanoic acid 是一种半抗原，包被 Atrazine-3-mercaptopropanoic acid 的多克隆抗体 (PcAb) 的 IC50 值为 7.5 ng mL。

Docosahexaenoic acid is a nutritionally-derived ω-3 fatty acid that is abundant in the brain and the retina and is thought to be important in early development and for therapeutic approaches to inflammatory disorders and cancer. 14(S)-HDHA is an oxygenation product of DHA that serves as a precursor to maresin 1 , an anti-inflammatory, pro-resolving mediator that prevents polymorphonuclear neutrophil (PMN) infiltration and stimulates macrophage phagocytosis. At doses as low as 0.2 ng/mouse 14(S)-HDHA administration resulted in reduced infiltration of PMNs into sites of inflammation.

Resolvins are a family of potent lipid mediators derived from both eicosapentaenoic acid and docosahexaenoic acid.[1] In addition to being anti-inflammatory, resolvins promote the resolution of the inflammatory response back to a non-inflamed state.[2] Resolvin D1 is produced physiologically from the sequential oxygenation of DHA by 15- and 5-lipoxygenase.[1] 17(R)-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human polymorphonuclear leukocyte (PMN) transendothelial migration, the earliest event in acute inflammation, with equipotency to RvD1 (EC50 = ~30 nM).[3] 17(R)-RvD1 exhibits a dose-dependent reduction in leukocyte infiltration in a mouse model of peritonitis with maximal inhibition of ~35% at a 100 ng dose.[3] In contrast to RvD1, the aspirin-triggered form resists rapid inactivation by eicosanoid oxidoreductases. Analytical and biological comparisons of synthetic 17(R)-RvD1 with endogenously derived 17(R)-RvD1 have confirmed its identity as matching the natural product.[4]

PDE5-IN-3 (compound 11j) 是一种 PDE5 的有效抑制剂 (IC50: 1.57 nM)。PDE5-IN-3 对 EGFR 具有中度抑制作用 (IC50: 5.827 μM)。PDE5-IN-3 明显抑制 Wnt β-catenin 通路，其 IC50 值为 1286.96 ng mL。PDE5-IN-3 在 HepG2 细胞中诱导内在的凋亡线粒体途径。PDE5-IN-3 表现出显著的抗肿瘤效果。

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

Resolvin D2 n-3 DPA (RvD2 n-3 DPA) is a specialized pro-resolving mediator (SPM).1It is formed from docosapentaenoic acid , an intermediate in the conversion of eicosapentaenoic acid to docosahexaenoic acid , in human leukocytes. RvD2 n-3 DPA (1 nM) reduces TNF-α-induced chemotaxis and adhesion of isolated human neutrophils.In vivo, RvD2 n-3 DPA (100 ng animal; i.v.) reduces peritoneal neutrophil infiltration and exudate levels of IL-6 and chemokine (C-C motif) ligand 2 (CCL2) in a mouse model of zymosan-induced inflammation. 1.Dalli, J., Colas, R.A., and Serhan, C.N.Novel n-3 immunoresolvents: Structures and actionsSci. Rep.31940(2013)

Callosobruchusic acid is an insect pheromone and monoterpene that has been found as a component of the copulation release pheromone erectin in azuki bean weevils (C. chinensis).1It induces copulation release activity in male azuki bean weevils (EC50= 6.5 ng insect). 1.Mori, K., Ito, T., Tanaka, K., et al.Synthesis and biological activity of optically active forms of (E)-3, 7-dimethyl-2-octene-1, 8-dioic acid (callosobruchusic acid): A component of the copulation release pheromone (erectin) of the azuki bean weevilTetrahedron39(13)2303-2306(1983)