Target Information

Target General Infomation
Target ID
T99948
Former ID
TTDNC00468
Target Name
Programmed cell deathe?Y? ligand 1 (PD-L1)
Gene Name
CD274
Synonyms
B7 homolog 1; B7H1; PDCD1 ligand 1; PDL1; Programmed cell death 1 ligand 1; Programmed death ligand 1; CD274
Target Type
Successful
Disease Advanced or metastatic urothelial carcinoma [ICD10: C67]
Bladder cancer [ICD9: 188; ICD10: C67]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Diffuse large B-cell lymphoma [ICD9: 200; ICD10: C83.3]
HIV-1 infection; Solid tumours [ICD9:001-139, 042, 140-199, 210-229; ICD10: B20-B24, C00-D48]
Metastatic melanoma [ICD9: 172; ICD10: C43]
Merkel cell carcinoma [ICD10: C4A]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Urothelial carcinoma [ICD10: C00-D49]
Function
Involved inthe costimulatory signal, essential for T- cell proliferation and production of IL10 and IFNG, in an IL2- dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.
BioChemical Class
Immunoglobulin
UniProt ID
Q9NZQ7
Sequence
MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEME
DKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGG
ADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTT
TTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERTH
LVILGAILLCLGVALTFIFRLRKGRMMDVKKCGIQDTNSKKQSDTHLEET
Drugs and Mode of Action
Drug(s) Avelumab Drug Info Approved Merkel cell carcinoma [889446]
Durvalumab Drug Info Approved Advanced or metastatic urothelial carcinoma [889446]
RG-7446 Drug Info Approved Urothelial carcinoma [889440]
Avelumab Drug Info Phase 3 Cancer [525127]
MEDI4736 Drug Info Phase 3 Solid tumours [524965], [542899]
MPDL-3280A Drug Info Phase 3 Metastatic melanoma [525141], [542904]
RG-7446 Drug Info Phase 3 Bladder cancer [549279]
Pidilizumab Drug Info Phase 2 Diffuse large B-cell lymphoma [523594], [525398], [542669]
Anti-PD-L1 Drug Info Phase 1 HIV-1 infection; Solid tumours [523665]
Modulator Durvalumab Drug Info [556264]
MEDI4736 Drug Info [550491]
MPDL-3280A Drug Info [544402]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cell adhesion molecules (CAMs)
Reactome PD-1 signaling
WikiPathways Costimulation by the CD28 family
References
Ref 523594ClinicalTrials.gov (NCT01420965) Sipuleucel-T, CT-011, and Cyclophosphamide for Advanced Prostate Cancer. U.S. National Institutes of Health.
Ref 523665ClinicalTrials.gov (NCT01455103) Phase 1 Biomarker Study of Anti-PDL-1 in Advanced Melanoma. U.S. National Institutes of Health.
Ref 524965ClinicalTrials.gov (NCT02273375) Double Blind Placebo Controlled Controlled Study of Adjuvant MEDI4736 In Completely Resected NSCLC. U.S. National Institutes of Health.
Ref 525127ClinicalTrials.gov (NCT02395172) Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200). U.S. National Institutes of Health.
Ref 525141ClinicalTrials.gov (NCT02409355) A Study of MPDL3280A Compared With Gemcitabine + Cisplatin or Carboplatin in Patients With Stage IV Squamous Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 525398Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013 Nov 20;31(33):4199-206.
Ref 542669(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7692).
Ref 542899(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7985).
Ref 542904(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7990).
Ref 549279Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034572)
Ref 8894402016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. doi: 10.1038/nrd.2017.14.
Ref 889446Drugs@FDA (Edaravone)
Ref 531481PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother. 2011 Jun;34(5):409-18.
Ref 531933Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65.
Ref 533256Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells. Cancer Immunol Res. 2015 Oct;3(10):1148-57.
Ref 544363PD-1 as a potential target in cancer therapy. Cancer Med. 2013 October; 2(5): 662-673.
Ref 544402Targeted immunotherapy for non-small cell lung cancer. World J Clin Oncol. 2014 May 10; 5(2): 39-47.
Ref 550491National Cancer Institute Drug Dictionary (drug id 740856).
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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