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notch receptor 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2861

Nomenclature: notch receptor 1

Family: Notch receptors

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 2555 9q34.3 NOTCH1 notch receptor 1
Mouse 1 2531 2 18.91 cM Notch1 notch 1
Rat 1 2531 3p13 Notch1 notch receptor 1
Previous and Unofficial Names Click here for help
notch 1 | Notch (Drosophila) homolog 1 (translocation-associated) | TAN1
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
IMR-1 Small molecule or natural product Hs Binding 5.0 pKd 1
pKd 5.0 (Kd 1.1x10-5 M) [1]
Description: Binding affinity for hNOTCH1 intracellular domain determined by SPR.
Inhibitor Comments
CB-103 is a small molecule that binds to the cleaved NOTCH1 receptor intracellular domain (NICD) that translocates to the nucleus and is a component of the functional nuclear NOTCH transcriptional activation complex. By inhibiting NOTCH-mediated transcriptional activation, CB-103 brings about anti-tumour effects in cancer cells that are driven by dominant active NICD.
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
brontictuzumab Peptide Hs Binding 8.4 pKd 5
pKd 8.4 (Kd 4.33x10-9 M) [5]
Immunopharmacology Comments
NOTCH1 and its ligand Delta-like 4 (DLL4) play a dominant role in mediating the effects of Notch signaling in T cells during Graft-versus-host disease (GvHD). Anti-NOTCH1 or anti-DLL4 antibodies controlled GvHD [8]. Anti-NOTCH1 was associated with dose-limiting toxicity; anti-DLL4 was not.

Activating mutations in NOTCH1 are one of the most frequent somatic alterations detected in chronic lymphocytic leukemia (CLL), and such mutations are associated with poor prognosis [6-7,9]. The mutations found in CLL generally affect the PEST domain of the receptor, are not ongogenic in isolation and are NOTCH ligand dependent. Different NOTCH1 mutations are found in T-acute lymphoblastic leukemia (T-ALL) [2], and these are more likely to lead to constitutive, ligand-independent NOTCH pathway activation.
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Inflammation
Immuno Process:  Tissue repair
Immuno Process:  Cytokine production & signalling
General Comments
NOTCH1 is a single-pass transmembrane receptor protein that controls T-cell differentiation. Gain-of-function mutations in NOTCH1 are present in >50% of human T-cell acute lymphoblastic leukemias (T-ALL) [3-4].


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1. Astudillo L, Da Silva TG, Wang Z, Han X, Jin K, VanWye J, Zhu X, Weaver K, Oashi T, Lopes PE et al.. (2016) The Small Molecule IMR-1 Inhibits the Notch Transcriptional Activation Complex to Suppress Tumorigenesis. Cancer Res, 76 (12): 3593-603. [PMID:27197169]

2. Belver L, Ferrando A. (2016) The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat Rev Cancer, 16 (8): 494-507. [PMID:27451956]

3. Bhanushali AA, Babu S, Thangapandi VR, Pillai R, Chheda P, Das BR. (2010) Mutations in the HD and PEST domain of Notch-1 receptor in T-cell acute lymphoblastic leukemia: report of novel mutations from Indian population. Oncol Res, 19 (2): 99-104. [PMID:21302811]

4. Grabher C, von Boehmer H, Look AT. (2006) Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer, 6 (5): 347-59. [PMID:16612405]

5. Gurney Al, Hoey TC, Bruhns MF, Axelrod FT. (2014) Notch1 receptor binding agents and methods of use thereof. Patent number: US20140011271A1. Assignee: Oncomed Pharmaceuticals. Priority date: 08/07/2008. Publication date: 09/01/2014.

6. Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, Escaramis G, Jares P, Beà S, González-Díaz M et al.. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature, 475 (7354): 101-5. [PMID:21642962]

7. Rossi D, Rasi S, Fabbri G, Spina V, Fangazio M, Forconi F, Marasca R, Laurenti L, Bruscaggin A, Cerri M et al.. (2012) Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood, 119 (2): 521-9. [PMID:22077063]

8. Tran IT, Sandy AR, Carulli AJ, Ebens C, Chung J, Shan GT, Radojcic V, Friedman A, Gridley T, Shelton A et al.. (2013) Blockade of individual Notch ligands and receptors controls graft-versus-host disease. J Clin Invest, 123 (4): 1590-604. [PMID:23454750]

9. Villamor N, Conde L, Martínez-Trillos A, Cazorla M, Navarro A, Beà S, López C, Colomer D, Pinyol M, Aymerich M et al.. (2013) NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia, 27 (5): 1100-6. [PMID:23295735]

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