to-188

Tazanolast is a selective mast-cell-stabilizing drug.

Jagged-1 (188-204) TFA(219127-21-6 free base) 是 JAG-1 蛋白的一个片段。 JAG-1 是 Notch 配体，是一种在皮肤中表达最明显的肽。 JAG-1 诱导表皮成熟。将淹没的角质形成细胞单层暴露于钙浓度升高的 JAG-1 会产生具有 loricrin 表达和 NF-alphaB 激活的分层。

Jagged-1 （188-204） 是 JAG-1 蛋白的一个片段。其中 JAG-1 能够诱导单核细胞衍生的人树突状细胞成熟，是一种在培养的和原发性多发性骨髓瘤细胞中高度表达的 Notch 配体。

DL-threo-2-methylisocitrate is a substrate of isocitrate lyase 1 (ICL1). Using Michaelis-Menten nonlinear least squares fitting, the kcat value was determined to be 5.24 s-1, and the Km of the purified recombinant ICL1 for threonine-D(s)L(s)-isocitrate (ICA) was 188 μM.

dl-threo-2-methylisocitrate is a substrate of isocitrate lyase 1 (ICL1). IC50 value: target: using michael-menten nonlinear least squares fitting to determine the purified recombinant ICL1's Km for threo-D(s)L(s)-isocitrate (ICA) is 188°M and kcat is 5.24

Insulin-degrading enzyme (IDE) is a thiol-sensitive zinc-metallopeptidase that acts as the major insulin-degrading protease in vivo, mediating the termination of insulin signaling. [1] In addition to regulating insulin action in diabetes pathogenesis, IDE plays a role in Varicella-Zoster virus infection and degradation of amyloid-β, a peptide implicated in Alzheimer's disease. ML-345 is a small molecule inhibitor that selectively targets cysteine819 in IDE with an EC50 value of 188 nM. [2] It demonstrates 10-fold selectivity for IDE over a panel of enzymes with reactive cysteine residues.[2] Reference：[1]. Maianti, J.P., McFedries, A., Foda, Z.H., et al. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Nature 511(7507), 94-98 (2014).[2]. Bannister, T.D., Wang, H., Abdul-Hay, S.O., et al. ML345, a small-molecule inhibitor of the insulin-degrading enzyme (IDE). 1 R03 DA024888-01 (MLSCN cycle 6), 1-41 (2014).

Resolvin conjugate in tissue regeneration 1 (RCTR1) is a specialized pro-resolving mediator (SPM) biosynthesized from docosahexaenoic acid by isolated human macrophages and apoptotic polymorphonuclear (PMN) neutrophils.1It has been found in human spleen and bone marrow.2RCTR1 is produced via lipoxygenase-mediated oxidation of DHA to 7(S)-8-epoxy-17(S)-HDHA, which is conjugated to glutathione.1,2,3RCTR1 (10 nM) increases phagocytosis ofE. colior apoptotic neutrophils in isolated human monocyte-derived macrophages.2It decreases chemotaxis induced by leukotriene B4in isolated human neutrophils when used at a concentration of 10 nM. RCTR1 (1 and 10 nM) accelerates tissue regeneration in planaria. Intraperitoneal administration of RCTR1 (100 ng/animal) shortens the inflammatory resolution period and decreases inflammatory exudate neutrophil infiltration in a mouse model ofE. coli-induced peritonitis. 1.Dalli, J., Ramon, S., Norris, P.C., et al.Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathwaysFASEB J.29(5)2120-2136(2015) 2.de la Rosa, X., Norris, P.C., Chiang, N., et al.Identification and complete stereochemical assignments of the new resolvin conjugates in tissue regeneration in human tissues that stimulate proresolving phagocyte functions and tissue regenerationAm. J. Pathol.188(4)950-966(2018) 3.Rodriguez, A.R., and Spur, B.W.First total synthesis of pro-resolving and tissue-regenerative resolvin sulfido-conjugatesTetrahedron Lett.58(16)1662-1668(2017)

Quorum sensing is a regulatory process used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group) and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[3] C16:1-Δ9-(L)-HSL is a long-chain AHL that functions as a quorum sensing signaling molecule in strains of S. meliloti.[4],[5],[6],[7] Regulating bacterial quorum sensing signaling can be used to inhibit pathogenesis and thus, represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[8] Reference：[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing. Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry. J. Bacteriol. 188(2), 773-783 (2006).[3]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions. FEBS Lett. 580(2), 561-567 (2006).[4]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium. Archives of Microbiology 180, 494-497 (2003).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti. Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Marketon, M.M., Glenn, S.A., Eberhard, A., et al. Quorum sensing controls exopolysaccharide production in Sinorhizobium meliloti. Journal of Bacteriology 185(1), 325-331 (2003).[7]. Marketon, M., Gronquist, M.R., Eberhard, A., et al. Characterization of the Sinorhizobium meliloti sinR sinI locus and the production of novel N-Acyl homoserine lactones. Journal of Bacteriology 184(20), 5686-5695 (2002).[8]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6(1), 17-27 (2008).

Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). Regulation of bacterial quorum sensing signaling systems to inhibit pathogenesis represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[3] AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group), and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[4] C16-HSL is one of a number of lipophilic, long acyl side-chain bearing AHLs, including its monounsaturated analog C16:1-(L)-HSL, produced by the LuxI AHL synthase homolog SinI involved in quorum-sensing signaling in S. meliloti, a nitrogen-fixing bacterial symbiont of certain legumes.[5],[6] C16-HSL is the most abundant AHL produced by the proteobacterium R. capsulatus and activates genetic exchange between R. capsulatus cells.[7] N-Hexadecanoyl-L-homoserine lactone and other hydrophobic AHLs tend to localize in relatively lipophilic cellular environments of bacteria and cannot diffuse freely through the cell membrane. The long-chain N-acylhomoserine lactones may be exported from cells by efflux pumps or may be transported between communicating cells by way of extracellular outer membrane vesicles.[8],[9]Reference:[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry Journal of Bacteriology 188(2), 773-783 (2006).[3]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies Nature Reviews.Microbiology 6(1), 17-27 (2008).[4]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions FEBS Letters 580, 561-567 (2006).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium Archives of Microbiology 180, 494-497 (2003).[7]. Schaefer, A.L., Taylor, T.A., Beatty, J.T., et al. Long-chain acyl-homoserine lactone quorum-sensing regulation of Rhodobacter capsulatus gene transfer agent production Journal of Bacteriology 184(23), 6515-6521 (2002).[8]. Pearson, J.P., Van Delden, C., and Iglewski, B.H. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals Journal of Bacteriology 181(4), 1203-1210 (1999).[9]. Mashburn-Warren, L., and Whiteley, M. Special delivery: Vesicle trafficking in prokaryotes Molecular Microbiology 61(4), 839-846 (2006).

Tyrosinase-related Protein 2 (TRP-2) (181-188) is a peptide derived from the tyrosinase-related protein 2 (TRP-2), specifically corresponding to residues 180-188. It is the primary epitope within TRP-2 that is recognized by anti-B16 CTLs. Moreover, It is a peptide that conforms to the binding motif of the MHC class I H2-Kb.

GAD65 (206-220) is a synthetic peptide derived from glutamic acid decarboxylase (GAD) 65, specifically corresponding to residues 180-188. It is known that GAD65 interacts with I-Ag7 MHC class II molecules and is a significant pancreatic antigen that self-reactive T cells target in type I diabetes mellitus.

Poloxamer 188 是一种非离子三嵌段共聚物表面活性剂，也是一种生物活性赋性剂，可用作医用辅料，可加剧 5XFAD 小鼠的脑淀粉样变性、突触前营养不良和致病性小胶质细胞活化。

Purinostat mesylate 是一种选择性的 HDAC 抑制剂。Purinostat mesylate 能够抑制 I 型和 IIb 型 HDACs (IC50: 0.81-11.5 nM)。Purinostat mesylate 能够影响LAMA84 和 188 BL-2 细胞的细胞周期，并诱导其凋亡，在体内显示出较强的抗白血病效果。Purinostat mesylate 能够用于研究淋巴细胞白血病。

XL-188 is a highly potent and selective inhibitor of USP7. XL188 inhibited USP7 catalytic domain and full-length enzyme with IC50 values of 193 and 90 nM, respectively. XL188 Promotes USP7-Dependent Loss of HDM2 and Increase of p53 and p21. XL188 represents one of only a small set of mammalian DUB inhibitors with low nanomolar potency and a high degree of selectivity relative to other DUBs

Talacotuzumab (JNJ 56022473) 是一种含有修饰的 Fc 结构的IgG1 型完全人源化的 CD123 中和单克隆抗体。Talacotuzumab 对 CD123、CD32b c、CD16-158F、CD16-158V 具有很高的亲和力， KD 分别为 0.43 nM、188 nM、46 nM、16.8 nM。Talacotuzumab 通过抑制 IL-3 与 CD123 结合进而抑制靶细胞中的 IL-3 信号传导。Talacotuzumab 诱导 Fc 区发生突变以增加对 CD16 (FcγRIIIa) 的亲和力，从而加强抗体依赖性细胞介导的细胞毒性 (ADCC)。Talacotuzumab 急性髓性白血病 (AML) 异种移植小鼠模型中抑制白血病细胞生长。

Letaplimab (IBI-188) 是一种靶向 CD47 的人源化IgG4类抗体，常联合阿扎胞苷治疗初诊中高危骨髓增生异常综合症。