GSK1995057 

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^{[1][2][3][4][5]}.

VHH-IgG1

Human IgG1 kappa, Isotype Control

Human

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.

GSK1995057 (0.043-4.7 mg; nebulized; single dose) potently attenuates pulmonary inflammation, endothelial injury, and alveolar-capillary leak in a dose-dependent manner in LPS-challened cynomolgus monkeys, with significant reductions in BALF neutrophils, proinflammatory cytokines, and injury markers observed at doses as low as 0.043 mg^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

7132  [NCBI]

P19438

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

78.24 kDa

Liquid

Colorless to light yellow

[GSK1995057]

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

Please store the product under the recommended conditions in the Certificate of Analysis.

• 
  Immobilized Human TNFR1 Protein, His Tag can bind GSK1995057. The EC₅₀ for this effect is 189.3 ng/mL.

• [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]