Cat. No.
MABL-2503
Application
SPR, therapeutic, Block, FC
Isotype
Engineer antibody
Species Reactivity
Human, Mouse
Clone No.
23814
From
Recombinant Antibody
Specificity
This antibody recognizes and binds both human and mouse notch 1 protein. This antibody does not cross react with other members of the notch family like notch 2 or notch 3. This antibody binds the ligand-binding domain of the Notch1 receptor that specifically blocks ligand-induced activation.
Alternative Names
Notch1; hN1; TAN-1; Neurogenic locus notch homolog protein 1; Translocation-associated notch protein TAN-1
UniProt
P46531
Immunogen
The original antibody was isolated from a phage display library generated from a human B- cell donor and panning against biotinylated-recombinant mouse notch 1 EGF 11-12 concatemer as the target protein.
Application Notes
Surface plasmon resonance confirmed that the original human IgG1 version of antibody 23814 binds the extracellular domain of the human and mouse notch 1 with an affinity of Kd= 2.3 nM and 3.7 nM respectively. Flow cytometric analysis confirmed that 23814 specifically bound only human and mouse notch 1 expressed on surface of CHO cells, but not notch 2 or notch 3. This antibody blocked Notch1 function in vivo, inhibited functional angiogenesis, and inhibited tumor growth without causing gastrointestinal toxicity. The lack of toxicity allowed for combination of 23814 and the VEGFR inhibitor tivozanib, resulting in significant growth inhibition of several VEGFR inhibitor-resistant tumor models. Monotherapy with 23814 antibody resulted in potent tumor growth inhibition of Ki-168 PDX tumors. Addition of 23814 to tivozanib treatment resulted in significantly greater tumor necrosis, as well as increased induction of hypoxia genes, compared with tivozanib monotherapy (PMID: 25995436).
Antibody First Published
Proia et al. 23814, an inhibitory antibody of ligand-mediated notch1 activation, modulates angiogenesis and inhibits tumor growth without gastrointestinal toxicity. Mol Cancer Ther. (2015) Aug;14(8):1858-67. PMID:25995436
Note on publication
Describes the isolation and characterization of this antibody and its use in combination with VEGFR inhibitor tivozanib to inhibit the growth of several VEGFR inhibitor-resistant tumor models.
Size
100 μg Purified antibody.
Concentration
1 mg/ml.
Purification
Protein A affinity purified
Buffer
PBS with 0.02% Proclin 300.
Storage Recommendation
Store at 4⁰C for up to 3 months. For longer storage, aliquot and store at - 20⁰C.