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anti-ADAM17 (human), mAb (rec.) (blocking) (D1(A12)) (preservative free)

AG-27B-6000PF-C100 100 µg INQ
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Additional Information

Product Data
Synonyms TNF-α-converting Enzyme; Disintegrin and Metalloproteinase Domain-containing Protein 17; CD156b
Properties
Clone D1(A12)
Isotype Human IgG1
Source/Host E. coli
Immunogen/Antigen Recombinant human ADAM17 (TACE) ectodomain tagged to biotin.
Label/Conjugates Preservative Free
Application Functional Application (Blocking): Inhibits ADAM17 activity at 15μg/ml (200nM).
Optimal conditions should be determined individually for each application.
Crossreactivity Human
Specificity Recognizes the catalytic and non-catalytic domain of human ADAM17 (TACE) through its variable light (VL) domain and variable heavy (VH) domain, respectively. Does not bind recombinant mouse ADAM17 ectodomain.
Purity ≥95% (SDS-PAGE)
Purity Detail Protein A/G-affinity purified.
Endotoxin Content <0.001EU/μg
Concentration 1mg/ml
Formulation Liquid. In PBS.
Other Product Data This cross-domain human antibody is a selective ADAM17 (TACE) antagonist and provides a unique alternative to small molecule metalloprotease inhibition. ADAM multidomain topology was exploited by first isolating an inhibitory human antibody (D1) that bound ADAM17-specific non-catalytic 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 ADAM17 catalytic domain.
Accession Number UniProt ID P78536
Product Type Monoclonal Antibody
Shipping and Handling
Shipping BLUE ICE
Short Term Storage +4°C
Long Term Storage -20°C
Handling Advice Avoid freeze/thaw cycles.
Use/Stability Stable for at least 1 year after receipt when stored at -20°C.
Documents
MSDS Download Document Download

Product Description

ADAM17 (Disintegrin and metalloproteinase domain-containing protein 17), also called TACE (Tumor necrosis factor-α-converting enzyme) is the prototype of the ADAM family of ectodomain shedding proteases (sheddase). ADAM17 is understood to be involved in the processing of TNF-α at the surface of the cell and from within the intracellular membranes of the trans-Golgi network. This process involves the cleavage and release of a soluble ectodomain from membrane-bound pro-proteins (such as pro-TNF-α) and is of known physiological importance. ADAM17 is responsible for the processing of a diverse variety of membrane-anchored cytokines, cell adhesion molecules, receptors, ligands and enzymes, including cleaving epidermal growth factor receptor (EGFR) ligands and extracellular Notch1. The proteolytic cleavage is an indispensable activation event for many of these substrates, ADAM17 has emerged as an attractive therapeutic target for the treatment of inflammatory diseases (e.g. rheumatoid arthritis) or inflammation associated cancer.

Product References

  1. Cross-domain inhibition of TACE ectodomain: C.J. Tape, et al.; PNAS 108, 5578 (2011)
  2. Anti-tumour effects of a specific anti-ADAM17 antibody in an ovarian cancer model in vivo: F.M. Richards, et al.; PLoS One e40597 (2012)
  3. iRHOM2 is a critical pathogenic mediator of inflammatory arthritis: P.D. Issuree, et al.; J. Clin. Invest. 123, 928 (2013)
  4. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17): R. Romee, et al.; Blood 121, 3599 (2013)
  5. Development of a 'mouse and human cross-reactive' affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy: H.F. Kwok, et al.; Protein Eng. Des. Sel. 27, 179 (2014)
  6. Targeting the sheddase activity of ADAM17 by an anti-ADAM17 antibody D1(A12) inhibits head and neck squamous cell carcinoma cell proliferation and motility via blockage of bradykinin induced HERs transactivation: Y. Huang, et al.; Int. J. Biol. Sci. 10, 702 (2014)
  7. Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells: F. Caiazza, et al.; Br. J. Cancer 112, 1895 (2015)
  8. Recent advances in the field of anti-cancer immunotherapy: H. Neves & H.F. Kwok; BBA Clinical 3, 280 (2015) (Review)
D1(A12) IgG inhibits constitutive shedding of TNF-&alpha; from IGROV1 (human ovarian cancer cell line) into culture medium. Medium was collected after 48 hours of incubation with or without IgGs at 200nM.
D1(A12) IgG inhibits constitutive shedding of TNF-α from IGROV1 (human ovarian cancer cell line) into culture medium. Medium was collected after 48 hours of incubation with or without IgGs at 200nM.
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