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Catalogue Number 152045
Applications Fn
Antigen/Gene or Protein Targets TACE (ADAM17)
Reactivity Human
Relevance TACE (CD156b) has proved capable of cleaving epidermal growth factor receptor (EGFR) ligands, extracellular Notch1, cell-surface receptors, and adhesion molecules. As proteolytic cleavage is an indispensable activation event for many of these substrates, TACE has emerged as an attractive therapeutic target for the treatment of cancer and rheumatoid arthritis. This “cross-domain” human antibody is a selective TACE antagonist and provides a unique alternative to smallmolecule metalloprotease inhibition.
Host Human
Immunogen Recombinant human ADAM17 (TACE) ectodomain tagged to biotin.
Subclass IgG1
Formulation PBS
Concentration 5.9mg/ml
Positive Control Brain, heart, kidney, liver, lung and spleen
Research Area Cancer, Cell Signaling & Signal Transduction, Metabolism, Neurobiology, Stem Cell Biology
Notes ADAM multidomain topology was exploited by first isolating an inhibitory human antibody (D1) that bound TACE-specific noncatalytic regions exclusively through its variable heavy (VH) domain. A D1-VH biased scFv phage-display library was then used to selectively isolate a new variable light (VL) chain that could simultaneously bind to the TACE catalytic domain. The resulting “cross-domain” human IgG1 antibody [D1(A12)] is a previously undescribed biochemically holistic ADAM ectodomain inhibitor and demonstrates a unique alternative to small-molecule metalloprotease inhibition.

D1(A12) only binds to the human form of TACE not to mouse. Ki: 0.27+/- 0.03nM against hADAM17.

Note from inventor: "D1(A12) is conformation sensitive and sees only a specific form of the native enzyme (reflecting its redox state). It does not work by IHC or WB. It was designed as a potential drug, active in native situations".

References: 8 entries

Caiazza et al. 2015. Br J Cancer. 112(12):1895-903. PMID: 26010411.

Fn

Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells.

Europe PMC ID: 26010411

Issuree et al. 2013. J Clin Invest. 123(2):928-32. PMID: 23348744.

Fn

iRHOM2 is a critical pathogenic mediator of inflammatory arthritis.

Europe PMC ID: 23348744

Anti-tumour effects of a specific anti-ADAM17 antibody in an ovarian cancer model in vivo.

Europe PMC ID: 22792380

Richards et al. 2012. PLoS One. 7(7):e40597. PMID: 22792380.

Fn

Tape et al. 2011. Proc Natl Acad Sci U S A. 108(14):5578-83. PMID: 21415364.

Fn

Cross-domain inhibition of TACE ectodomain.

Europe PMC ID: 21415364


Add a reference

References: 8 entries

Caiazza et al. 2015. Br J Cancer. 112(12):1895-903. PMID: 26010411.

Fn

Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells.

Europe PMC ID: 26010411

Issuree et al. 2013. J Clin Invest. 123(2):928-32. PMID: 23348744.

Fn

iRHOM2 is a critical pathogenic mediator of inflammatory arthritis.

Europe PMC ID: 23348744

Anti-tumour effects of a specific anti-ADAM17 antibody in an ovarian cancer model in vivo.

Europe PMC ID: 22792380

Richards et al. 2012. PLoS One. 7(7):e40597. PMID: 22792380.

Fn

Tape et al. 2011. Proc Natl Acad Sci U S A. 108(14):5578-83. PMID: 21415364.

Fn

Cross-domain inhibition of TACE ectodomain.

Europe PMC ID: 21415364


Add a reference

References: 8 entries

Caiazza et al. 2015. Br J Cancer. 112(12):1895-903. PMID: 26010411.

Fn

Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells.

Issuree et al. 2013. J Clin Invest. 123(2):928-32. PMID: 23348744.

Fn

iRHOM2 is a critical pathogenic mediator of inflammatory arthritis.

Anti-tumour effects of a specific anti-ADAM17 antibody in an ovarian cancer model in vivo.

Richards et al. 2012. PLoS One. 7(7):e40597. PMID: 22792380.

Fn

Tape et al. 2011. Proc Natl Acad Sci U S A. 108(14):5578-83. PMID: 21415364.

Fn

Cross-domain inhibition of TACE ectodomain.


Add a reference


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