to-188

Tazanolast, a selective mast-cell-stabilizing drug, inhibits the release of chemical mediators (histamine and leukotrienes) from mast cells, reduces inflammation, and is used in the treatment of allergic disorders, such as asthma and allergic rhinitis.

Jagged-1 (188-204) TFA(219127-21-6 free base) is a fragment of the JAG-1 protein. JAG-1 is Notch ligand, a peptide that is the most conspicuously expressed ligand in skin. JAG-1 induces epidermal maturation. Exposing submerged keratinocytes monolayers to JAG-1 with elevated calcium concentration produces stratification with loricrin expression and NF-alphaB activation.

DL-threo-2-methylisocitrate is a substrate of isocitrate lyase 1 (ICL1). Using Michaelis-Menten nonlinear least squares fitting, the kcat value was 1.25 s-1 and the Km was 718 μM. In comparison, the Km of threonine-D(s)L(s)-isocitrate (ICA) was 188 μM and the kcat was 5.24 s-1.

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 TRP-2, specifically corresponding to residues 180-188, and it is the primary epitope within TRP-2 recognized by anti-B16 CTLs. Additionally, it 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 is a nonionic triblock copolymer surfactant and bioactive excipient used as a medical excipient to exacerbate cerebral amyloidosis, presynaptic dystrophy, and pathogenic microglial cell activation in 5XFAD mice.

Purinostat mesylate is a selective HDAC inhibitor. purinostat mesylate inhibits type I and type IIb HDACs (IC50: 0.81-11.5 nM). purinostat mesylate affects the cell cycle of LAMA84 and 188 BL-2 cells and induces apoptosis, showing a strong anti-leukaemic effect in vivo. purinostat mesylate has been used to study lymphocytic leukaemia. Purinostat mesylate can be used to study lymphocytic leukaemia.

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) is an IgG1 fully humanized CD123 neutralizing monoclonal antibody containing a modified Fc structure. Talacotuzumab has a high affinity for CD123, CD32b/c, CD16-158F and CD16-158V, with KD of 0.43 nM, 188 nM, 46 nM and 16.8 nM, respectively. Talacotuzumab inhibits IL-3 signaling in target cells by inhibiting IL-3 binding to CD123. Talacotuzumab induces mutations in the Fc region to increase affinity for CD16 (FCγriiia), thereby enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Talacotuzumab inhibits leukemia cell growth in xenografted mouse models of acute myeloid leukemia (AML).

Letaplimab (IBI-188) is a humanized IgG4 class antibody targeting CD47 and is often used in combination with azacitidine for the treatment of primary diagnosis of intermediate- to high-risk myelodysplastic syndromes.

Jagged-1 (188-204)is a fragment of the JAG-1 protein. JAG-1 is Notch ligand, a peptide that is the most conspicuously expressed ligand in skin. JAG-1 induces epidermal maturation. Exposing submerged keratinocytes monolayers to JAG-1 with elevated calcium concentration produces stratification with loricrin expression and NF-αB activation.