- References (2)
- Inventor Info
|Antigen/Gene or Protein Targets||TACE (ADAM17)|
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.
|Immunogen||Recombinant human ADAM17 (TACE) ectodomain tagged to biotin.|
|Positive Control||Brain, heart, kidney, liver, lung and spleen|
|Research Area||Cancer, Cell Signaling & Signal Transduction, Metabolism, Neurobiology, Stem Cell Biology|
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. This product is the mouse IgG engineered version. The variable domain is the same as the original D1(A12) product in related products.
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".
Recombinant monoclonal antibody with mouse IgG produced from the original human recombinant monoclonal. Manufactured using Absolute Antibody’s Recombinant Platform with variable regions (i.e. specificity) from the phage display antibody D1 (A12).
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