programmed cell death 1 (CD279) | Other immune checkpoint proteins | IUPHAR Guide to IMMUNOPHARMACOLOGY

Top ▲

programmed cell death 1 (CD279)

Target id: 2760

Nomenclature: programmed cell death 1 (CD279)

Abbreviated Name: PD-1

Family: Other immune checkpoint proteins, CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: ON :     programmed cell death 1 (CD279) has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 288 2q37.3 PDCD1 programmed cell death 1
Mouse 1 288 1 D Pdcd1 programmed cell death 1
Rat 1 287 9q36 Pdcd1 programmed cell death 1
Previous and Unofficial Names
SLEB2
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the extracellular domain of human PD-1 (Apo-PD-1).
PDB Id:  3RRQ
Resolution:  2.1Å
Species:  Human
References: 
Natural/Endogenous Ligands
programmed cell death 1 ligand 1 {Sp: Human}

Download all structure-activity data for this target as a CSV file

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
pembrolizumab Hs Binding ~10.0 pKd 3
pKd ~10.0 (Kd ~1x10-10 M) [3]
BGB-A317 Hs Binding 9.8 pKd 4
pKd 9.8 (Kd 1.5x10-10 M) [4]
nivolumab Hs Binding 9.1 pKd 6,9-10
pKd 9.1 (Kd 7.3x10-10 M) [6,9-10]
Antibody Comments
The clinical potential of PD-1 blockade in immuno-oncology is reviewed in [9]. Binding affinity for BGB-A317 should be considered preliminary until reported in a peer reviewed article.
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
programmed cell death 1 ligand 1 {Sp: Human} Hs Binding - -
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
Role: 
References:  2
Disease:  Multiple sclerosis
Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
Disease:  Renal cell carcinoma
Disease Ontology: DOID:4450
Comments: 
References:  5
Disease:  Systemic lupus erythematosus, susceptibility to, 2; SLEB2
Synonyms: Systemic lupus erythematosus [Orphanet: ORPHA536] [Disease Ontology: DOID:9074]
Disease Ontology: DOID:9074
OMIM: 605218
Orphanet: ORPHA536
General Comments
The endogenous ligands for human PD-1 are programmed cell death 1 ligand 1 (PD-L1 aka CD274 (CD274, Q9NZQ7) and programmed cell death 1 ligand 2 (PD-L2; PDCD1LG2). These ligands are cell surface peptides, normally involved in immune system regulation.

References

Show »

1. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T. (1996) Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol., 8 (5): 765-72. [PMID:8671665]

2. Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, Matcovitch-Natan O, Kertser A, David E, Amit I, Schwartz M. (2016) PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat. Med., 22 (2): 135-7. [PMID:26779813]

3. Carven GJ, Van Eenennaam H, Dulos GJ. (2010) Antibodies to human programmed death receptor PD-1. Patent number: US20100266617. Assignee: Organon NV. Priority date: 13/06/2008. Publication date: 21/10/2010.

4. Desai J, Markman B, Sandhu SK, Gan HK, Friedlander M, Tran B, Meniawy T, Boolell V, Colyer D, Norris C et al.. A phase I dose-escalation study of BGB-A317, an anti-programmed death-1 (PD-1) mAb in patients with advanced solid tumors. Accessed on 06/06/2017. Modified on 06/06/2017. http://meetinglibrary.asco.org, http://meetinglibrary.asco.org/record/125804/abstract

5. FDA. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. Accessed on 18/04/2018. Modified on 18/04/2018. www.fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm604685.htm?utm_campaign=Oncology%204%2F16%2F2018&utm_medium=email&utm_source=Eloqua&elqTrackId=461a88586a9a4db284ceb54da34a6a23&elq=8b10e118e0b249beb2807c129fc264e8&elqaid=3169&elqat=1&elqCampaignId=2374

6. Hall RD, Gray JE, Chiappori AA. (2013) Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control, 20 (1): 22-31. [PMID:23302904]

7. Ishibashi N, Watanabe T, Kanehira M, Watanabe Y, Hoshikawa Y, Notsuda H, Noda M, Sakurada A, Ohkouchi S, Kondo T et al.. (2018) Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis. Surg. Today, 48 (7): 726-734. [PMID:29546496]

8. Johnson DB, Rioth MJ, Horn L. (2014) Immune checkpoint inhibitors in NSCLC. Curr Treat Options Oncol, 15 (4): 658-69. [PMID:25096781]

9. Kline J, Gajewski TF. (2010) Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Curr Opin Investig Drugs, 11 (12): 1354-9. [PMID:21154117]

10. Korman AJ, Srinivasan M, Wang C, Selby MJ, Chen B, Cardarelli JM. (2006) Human monoclonal antibodies to programmed death 1(pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics. Patent number: WO2006121168. Assignee: Ono Pharmaceutical Co. Priority date: 09/05/2005. Publication date: 02/03/2015.

11. Malas S, Harrasser M, Lacy KE, Karagiannis SN. (2014) Antibody therapies for melanoma: New and emerging opportunities to activate immunity (Review). Oncol. Rep., 32 (3): 875-86. [PMID:24969320]

12. Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS et al.. (2018) PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N. Engl. J. Med., 379 (4): 341-351. [PMID:29863979]

13. Pal SK, Hu A, Chang M, Figlin RA. (2014) Programmed death-1 inhibition in renal cell carcinoma: clinical insights and future directions. Clin Adv Hematol Oncol, 12 (2): 90-9. [PMID:24892254]

14. Yu Y, Tsang JC, Wang C, Clare S, Wang J, Chen X, Brandt C, Kane L, Campos LS, Lu L et al.. (2016) Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway. Nature, 539 (7627): 102-106. [PMID:27749818]

How to cite this page

Other immune checkpoint proteins: programmed cell death 1 (CD279). Last modified on 08/08/2018. Accessed on 16/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2760.