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CD38

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2766

Nomenclature: CD38

Family: Abscisic acid receptor complex, CD molecules

Contents:

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
Alphafold P28907 (Hs), Q4FJL8 (Mm), Q64244 (Rn)
ChEMBL Target CHEMBL4660 (Hs)
Ensembl Gene ENSG00000004468 (Hs), ENSMUSG00000029084 (Mm), ENSRNOG00000003069 (Rn)
Entrez Gene 952 (Hs), 12494 (Mm), 25668 (Rn)
Human Protein Atlas ENSG00000004468 (Hs)
KEGG Gene hsa:952 (Hs), mmu:12494 (Mm), rno:25668 (Rn)
OMIM 107270 (Hs)
Pharos P28907 (Hs)
RefSeq Nucleotide NM_001775 (Hs), NM_007646 (Mm), NM_013127 (Rn)
RefSeq Protein NP_001766 (Hs), NP_031672 (Mm), NP_037259 (Rn)
SynPHARM 82660 (in complex with isatuximab)
UniProtKB P28907 (Hs), Q4FJL8 (Mm), Q64244 (Rn)
Wikipedia CD38 (Hs)
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

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MK-0159 Small molecule or natural product Mm Inhibition 8.5 pIC50 8
⤷ pIC50 8.5 (IC50 3x10-9 M) [8]
MK-0159 Small molecule or natural product Hs Inhibition 7.7 pIC50 8
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [8]
View species-specific inhibitor tables
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 9
⤷ pKd 8.5 – 10.0 (Kd 3x10-9 – 1x10-10 M) [9]
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) [10], 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:   macrophage (CL:0000235)
monocyte (CL:0000576)
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)
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  Cytokine production & signalling

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. Lagu B, Wu X, Kulkarni S, Paul R, Becherer JD, Olson L, Ravani S, Chatzianastasiou A, Papapetropoulos A, Andrzejewski S. (2022) Orally Bioavailable Enzymatic Inhibitor of CD38, MK-0159, Protects against Ischemia/Reperfusion Injury in the Murine Heart. J Med Chem, 65 (13): 9418-9446. [PMID:35762533]

9. 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.

10. 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

Abscisic acid receptor complex: CD38. Last modified on 08/08/2022. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2766.