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CD38

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Target id: 2766

Nomenclature: CD38

Family: CD molecules, Abscisic acid receptor complex

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 300 4p15.32 CD38 CD38 molecule 7
Mouse 1 304 5 23.85 cM Cd38 CD38 antigen
Rat 1 303 14q21 Cd38 CD38 molecule
Previous and Unofficial Names Click here for help
ADP-ribosyl cyclase 1
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of CD38 with a novel CD38-targeting antibody SAR650984 (=isatuximab).
PDB Id:  4CMH
Ligand:  isatuximab
Resolution:  1.53Å
Species:  Human
References:  3

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Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
isatuximab Peptide Approved drug Primary target of this compound Hs Binding 8.5 – 10.0 pKd 8
pKd 8.5 – 10.0 (Kd 3x10-9 – 1x10-10 M) [8]
mezagitamab Peptide Immunopharmacology Ligand Hs Binding 8.3 pKd 4
pKd 8.3 (Kd 5.5x10-9 M) [4]
Description: Binding affinity of Ab79 for CD38 ectodomain, determined by Biacore SPR analysis.
daratumumab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Antagonist 8.2 pKd 2
pKd 8.2 (Kd 6.06x10-9 M) [2]
Immunopharmacology Comments
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [6]. Since CD38 is expressed in a subset of haematological tumours, particularly in plasma cell tumours such as multiple myeloma (MM), anti-CD38 monoclonal antibodies have been developed with immuno-oncology potential as their main indication. Daratumumab (a MM therapeutic) was the first-in-class anti-CD38 antibody to reach the clinic. Additional investigational CD38-targeting antibodies include isatuximab (SAR650984, ImmunoGen) [3], MOR202 (MorphoSys) [1], AT13/5 (Tenovus Research) [5] and mezagitamab (Takeda) [9], which were all primarily developed for MM and other haematological cancers. However, anti-CD38 monoclonals may have applications in the treatment of diseases in addition to haematological malignancies, including solid tumours and antibody-mediated autoimmune diseases.
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
macrophage (CL:0000235)
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Immuno Cell Type:  B cells
Immuno Cell Type:  T cells
Immuno Cell Type:  Natural killer cells
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0030890 positive regulation of B cell proliferation IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0030890 positive regulation of B cell proliferation IMP
GO:0050853 B cell receptor signaling pathway IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0030890 positive regulation of B cell proliferation IMP
GO:0050853 B cell receptor signaling pathway IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes, IEA only
GO:0034097 response to cytokine IEP
click arrow to show/hide IEA associations
GO:0070555 response to interleukin-1 IEA

References

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1. Chim CS, Kumar SK, Orlowski RZ, Cook G, Richardson PG, Gertz MA, Giralt S, Mateos MV, Leleu X, Anderson KC. (2018) Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia, 32 (2): 252-262. [PMID:29257139]

2. De Weers M, Graus Y, Oprins J, Parren P, Van De Winkel J, Van Vugt M. (2010) Antibodies Against Cd38 For Treatment Of Multiple Myeloma. Patent number: US7829673. Assignee: Genmab A/S. Priority date: 23/03/2005. Publication date: 09/11/2010.

3. Deckert J, Wetzel MC, Bartle LM, Skaletskaya A, Goldmacher VS, Vallée F, Zhou-Liu Q, Ferrari P, Pouzieux S, Lahoute C et al.. (2014) SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin. Cancer Res., 20 (17): 4574-83. [PMID:24987056]

4. Elias KA, Landes G, Singh S, Korver W, Drake AW, Haak-Frendscho M, Snell GP, Bhaskar V. (2012) Anti-cd38 antibodies. Patent number: WO2012092612A1. Assignee: Takeda Pharmaceutical Company Limited. Priority date: 30/12/2010. Publication date: 05/07/2012.

5. Ellis JH, Barber KA, Tutt A, Hale C, Lewis AP, Glennie MJ, Stevenson GT, Crowe JS. (1995) Engineered anti-CD38 monoclonal antibodies for immunotherapy of multiple myeloma. J. Immunol., 155 (2): 925-37. [PMID:7608568]

6. Hamblin TJ. (2003) CD38: what is it there for?. Blood, 102: 1939-1940. DOI: 10.1182/blood-2003-07-2332

7. Jackson DG, Bell JI. (1990) Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. J. Immunol., 144 (7): 2811-5. [PMID:2319135]

8. Park PU, Bartle L, Skaletskaya A, Golmakher V, Tavares D, Deckert J, Milol V, Blanc V. (2011) Novel anti-cd38 antibodies for the treatment of cancer. Patent number: US20110262454 A1. Assignee: Sanofi-Aventis. Priority date: 20/08/2015. Publication date: 27/10/2011.

9. Roepcke S, Plock N, Yuan J, Fedyk ER, Lahu G, Zhao L, Smithson G. (2018) Pharmacokinetics and pharmacodynamics of the cytolytic anti-CD38 human monoclonal antibody TAK-079 in monkey - model assisted preparation for the first in human trial. Pharmacol Res Perspect, 6 (3): e00402. [PMID:29864242]

How to cite this page

CD molecules: CD38. Last modified on 21/01/2020. Accessed on 24/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2766.