GSK1995057
Based on 1 Customer Validation
GSK1995057 is a human monoclonal antibody (mAb) targeting TNFRSF1A. GSK1995057 selectively binds to TNFR1, blocks the binding of TNF-α and LT-α, and does not interfere with TNFR2 signaling. GSK1995057 inhibits the activation of NF-κB, JNK and MAPK pathways, alleviates apoptosis (apoptosis) and inflammatory responses (inhibiting IL-1β, IL-6, IL-10, TNF-α), and prevents viability loss of human nucleus pulposus cells. GSK1995057 inhibits the expression of cytokines and neutrophil adhesion molecules in human pulmonary microvascular endothelial cell monolayers, and reduces inflammatory responses and lung injury symptoms in non-human primates. GSK1995057 forms complexes with HAVH autoantibodies, thereby activating TNFR1 and triggering the release of cytokines and IL-8 in human cells. GSK1995057 can be used in research related to intervertebral disc degeneration and acute lung injury.
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- Purity: 99.09%
- 분자량:131.32 kDa
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
VHH-hFc
Human
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TNFRSF1A |
GSK1995057 (10 nM; 12 h) significantly inhibits LPS (HY-D1056)-induced loss of cell viability in human nucleus pulposus cells, and attenuates cell apoptosis by regulating proteins of the extrinsic apoptotic pathway[2].
GSK1995057 (10 nM; 12 h) significantly inhibits LPS-induced secretion of pro-inflammatory and regulatory cytokines (IL-1β, IL-6, IL-10, TNF-α), suppresses the upregulated expression of extracellular matrix degrading enzyme genes (MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5), and blocks the activation of NF-κB, JNK and P38 MAPK signaling pathways in human nucleus pulposus cells[2].
GSK1995057 (10 nM; 1-4 h) potently inhibits TNF-α-stimulated neutrophil-endothelial cell interactions, endothelial permeability, adhesion molecule expression, and proinflammatory cytokine release in human lung microvascular endothelial cells (HMVEC-L) and human neutrophils[3].
GSK1995057 (0.00001-1 μM; 1 h serum incubation, 24 h cell incubation), upon binding to serum from anti-HAVH antibody-positive donors, activates TNFR1 and induces IL-8 release from MRC-5 human lung fibroblasts, human alveolar epithelial cells, and human primary lung fibroblasts in a concentration-dependent bell-shaped manner[4].
GSK1995057 binds with high affinity (1.65×10-10 M) to purified polyclonal HAVH autoantibodies[4].
GSK1995057 (0.00001-1 μM) induces TNF-R1 activation and IL-8 release in the human lung fibroblast cell line MRC-5 when mixed with human serum samples containing the co-existing specific autoantibodies against GSK2862277, with the activation effect peaking at 0.001 μM[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human nucleus pulposus cells (HNPCs)
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Concentration:10 nM
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Incubation Time:12 h
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Result:Significantly promoted cell viability in HNPCs and suppressed the LPS-induced decline in cell viability, resulting in a significantly higher OD value at 450 nm compared to the LPS + dummy dAb group.
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Cell Line:human nucleus pulposus cells (HNPCs)
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Concentration:10 nM
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Incubation Time:12 h (pre-incubated prior to LPS stimulation)
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Result:Significantly reduced the percentage of TUNEL-positive apoptotic cells in LPS-stimulated HNPCs, with the apoptosis rate decreasing from ~20% in the LPS + dummy dAb group to ~10% in the LPS + GSK1995057 group.
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Cell Line:human nucleus pulposus cells (HNPCs)
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Concentration:10 nM
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Incubation Time:12 h (pre-incubated prior to LPS stimulation)
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Result:Significantly reduced LPS-induced secretion of IL-1β, IL-6, IL-10, and TNF-α in HNPCs, with each cytokine level significantly lower than in the LPS + dummy dAb group.
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Cell Line:human nucleus pulposus cells (HNPCs)
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Concentration:10 nM
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Incubation Time:12 h (pre-incubated prior to LPS stimulation)
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Result:Significantly suppressed LPS-induced upregulation of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 mRNA expression in HNPCs, with each gene's expression level significantly lower than in the LPS + dummy dAb group.
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Cell Line:human nucleus pulposus cells (HNPCs)
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Concentration:10 nM
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Incubation Time:12 h (pre-incubated prior to LPS stimulation)
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Result:Significantly suppressed LPS-induced increases in the p-P65/P65 ratio, ASK1 expression, p-JNK/JNK ratio, and p-P38/P38 ratio in HNPCs.
Had no significant effect on the p-ERK/ERK ratio or total P65 expression in LPS-stimulated HNPCs.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:young adult[3]
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Dosage:0.043 mg; 0.45 mg; 4.7 mg
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Administration:nebulized; single dose
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Result:Markedly suppressed BALF neutrophil counts at 6 hours after LPS exposure.
Significantly suppressed BALF neutrophil counts at 24 hours at 0.45 mg and 4.7 mg doses.
Reduced BALF concentrations of myeloperoxidase, alpha-2-macroglobulin, von Willebrand factor, and proinflammatory cytokines IL-1β, IL-6, and IL-8.
Reduced BALF monocyte-macrophage numbers at 24 hours, reaching significance with 0.45 mg and 4.7 mg doses.
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
ELISA, FACS, Functional assay
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Immobilized Human TNFR1 Protein, His Tag can bind GSK1995057. The EC50 for this effect is 189.3 ng/mL.
Chemical Information
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Appearance Liquid
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분자량 131.32 kDa
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Color Colorless to light yellow
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SMILES
[GSK1995057]
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선적
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[1]. Liao K, et al. Detection of Memory B Activity Against a Therapeutic Protein in Treatment-Naïve Subjects. AAPS J. 2018;20(3):51. Published 2018 Mar 16. [Content Brief]
[2]. Lv F, et al. Inhibition of TNFR1 Attenuates LPS Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Regulating the NF-KB and MAPK Signalling Pathway. Neurochem Res. 2021;46(6):1390-1399. [Content Brief]
[3]. Proudfoot A, et al. Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury. Thorax. 2018;73(8):723-730. [Content Brief]
[4]. Holland MC, et al. Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-α receptor 1. J Clin Immunol. 2013;33(7):1192-1203. [Content Brief]
[5]. Cordy JC, et al. Specificity of human anti-variable heavy (VH ) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of tumour necrosis factor-α receptor 1. Clin Exp Immunol. 2015;182(2):139-148. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GSK1995057 Related Classifications
HY-P991400 Related Classifications
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