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OX-40 ligand

别名	glycoprotein Gp34, TXGP-1
Compound Class	Peptide
变动原因	OX40L (CD252) is the ligand for tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, a.k.a. OX40 or CD134). OX40 is a secondary co-stimulatory immune checkpoint molecule expressed on activated T cells (requiring CD28 co-stimulatory signal), and OX40L is expressed on activated dendritic cells. The OX40/OX40L pair is involved in late T-cell costimulatory signaling and both are transiently expressed following antigen recognition, and blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models . The OX40/OX40L pathway is being investigated for the development of novel anti-inflammatory therapeutics and anti-cancer drugs. An antibody binding mouse OX40L
Species	Human
Related Product	OX-40 ligand

Summary

基因/前体

Gene symbol	Gene name	Precursor protein name	Species	别名
TNFSF4	TNF superfamily member 4	prepro-tumor necrosis factor ligand superfamily member 4	Human	TXGP1, OX-40L, gp34, CD252, tax-transcriptionally activated glycoprotein 1, 34kD, tumor necrosis factor (ligand) superfamily, member 4, OX40L, CD134L, tumor necrosis factor superfamily member 4

是否批准为药物？

IUPAC Name

4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide

别名

glycoprotein Gp34, TXGP-1

数据库链接

UniProtKB	P23510
Wikipedia	OX40L
RCSB PDB Structure	2HEV
Ensembl Gene	ENSG00000117586

生物活性

生物活性评价	OX40L is overexpressed in B cells, T cells, and fibroblasts in fibrotic skin of patients with systemic sclerosis (SSc) . The authors suggest that soluble OX40L represents a promising biomarker predictive of worsening fibrosis in these patients. Their in vivo studies in mouse models of SSc indicate that antibody-driven blockade of OX40L protects against inflammatory skin, lung, and vessel fibrosis, and can induce regression of established dermal fibrosis. This mechanism is ineffective in preventing noninflammatory skin fibrosis in a mouse model. These studies used the mouse anti-OX40L monoclonal RM134L. Blockade of OX40L activity has also been reported to be effective against arthritis in mouse models of the disease .
关联靶标	OX40

临床资料

作用机制与药效学效应	Sulfonamides are structural analogues of 4-aminobenzoic acid (pABA) an intermediate in the de novo synthesis of folate by some prokaryotes, lower eukaryotes and plants . The antibacterial MMOA is competitive inhibition of bacterial dihydropteroate synthase (DHPS) resulting in a block of folate biosynthesis .

参考文献

1. Elhai M, Avouac J, Hoffmann-Vold AM, Ruzehaji N, Amiar O, Ruiz B, Brahiti H, Ponsoye M, Fréchet M, Burgevin A et al.. (2016) OX40L blockade protects against inflammation-driven fibrosis.. Proc Natl Acad Sci USA, 113 (27): (E3901-10). [PMID:27298374]
2. Komura K, Yoshizaki A, Kodera M, Iwata Y, Ogawa F, Shimizu K, Wayaku T, Yukami T, Murata M, Hasegawa M et al.. (2008) Increased serum soluble OX40 in patients with systemic sclerosis.. J Rheumatol, 35 (12): (2359-62). [PMID:18843780]
3. Gwyer Findlay E, Danks L, Madden J, Cavanagh MM, McNamee K, McCann F, Snelgrove RJ, Shaw S, Feldmann M, Taylor PC et al.. (2014) OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis.. Proc Natl Acad Sci USA, 111 (6): (2289-94). [PMID:24469824]
4. Webb GJ, Hirschfield GM, Lane PJ. (2016) OX40, OX40L and Autoimmunity: a Comprehensive Review.. Clin Rev Allergy Immunol, 50 (3): (312-32). [PMID:26215166]

结构

Peptide Sequence	MERVQPLEENVGNAARPRFERNKLLLVASVIQGLGLLLCFTYICLHFSALQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL
Post Translation Modifications	N-linked glycosylation of asparagine residue at position 152; predicted N-linked glycosylation of asparagines at positions 90, 114 and 157; disulphide bond formation between cysteine residues at positions 97 and 181

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