Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ13FT)

• DTT Name: T-cell-specific surface glycoprotein CD28 (CD28)
• Synonyms: TP44; CD28-S2
• Gene Name: CD28
• DTT Type: Successful target; [1]
• UniProt ID: CD28_HUMAN
• TTD ID: T85529
• Sequence:
  MLRLLLALNLFPSIQVTGNKILVKQSPMLVAYDNAVNLSCKYSYNLFSREFRASLHKGLD
  SAVEVCVVYGNYSQQLQVYSKTGFNCDGKLGNESVTFYLQNLYVNQTDIYFCKIEVMYPP
  PYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVR
  SKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS
• Function: Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation. Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells. Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  T cell receptor signaling pathway (hsa04660)
  Intestinal immune network for IgA production (hsa04672)
  Type I diabetes mellitus (hsa04940)
  Measles (hsa05162)
  Autoimmune thyroid disease (hsa05320)
  Systemic lupus erythematosus (hsa05322)
  Rheumatoid arthritis (hsa05323)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  CD28 co-stimulation (R-HSA-389356)
  CD28 dependent PI3K/Akt signaling (R-HSA-389357)
  CD28 dependent Vav1 pathway (R-HSA-389359)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Belatacept	DMXLYQF	Kidney transplant rejection	NE84	Approved	[1]

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AB-103	DMPDQ8T	Necrotizing soft tissue infection	1B71	Phase 3	[2]
Lulizumab pegol	DMGWZ93	Systemic lupus erythematosus	4A40.0	Phase 2	[3]
AU101	DMLAKPI	Osteosarcoma	2B51	Phase 1/2	[4]
REGN5668	DMH1UV5	Ovarian cancer	2C73	Phase 1/2	[5]
REGN5678	DM0Y6WU	Prostate cancer	2C82.0	Phase 1/2	[6]
CD19-CAR and CD28-CAR T Cells	DMUR1MN	Acute lymphoblastic leukaemia	2A85	Phase 1	[7]
CD28 and CD137 CAR-T Cells	DMFGQXB	Acute lymphoblastic leukaemia	2A85	Phase 1	[8]
RG6333	DM1BRF2	Non-hodgkin lymphoma	2B33.5	Phase 1	[9]
RO7443904	DMSWZNU	Non-hodgkin lymphoma	2B33.5	Phase 1	[10]
SAR442257	DMXD5QP	Malignant neoplasm	2A00-2F9Z	Phase 1	[11]
SAR443216	DMUQNG6	Gastric cancer	2B72	Phase 1	[12]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TGN-1412	DMELNA8	Autoimmune diabetes	5A10	Discontinued in Phase 1	[13]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anti-CD28	DM5BH7J	Immune System disease	4A01-4B41	Investigative	[14]
FR-104	DM7UP4E	Autoimmune diabetes	5A10	Investigative	[14]

References

• [1] New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT04590326) Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3). U.S.National Institutes of Health.
• [6] Clinical pipeline report, company report or official report of Regeneron Pharmaceuticals.
• [7] ClinicalTrials.gov (NCT02146924) Cellular Immunotherapy in Treating Patients With High-Risk Acute Lymphoblastic Leukemia
• [8] ClinicalTrials.gov (NCT02186860) Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With Acute Lymphoblastic Leukemia
• [9] Clinical pipeline report, company report or official report of Roche
• [10] Clinical pipeline report, company report or official report of Genentch
• [11] Clinical pipeline report, company report or official report of Sanofi.
• [12] Clinical pipeline report, company report or official report of Sanofi
• [13] TGN1412: From Discovery to Disaster. J Young Pharm. 2010 Jul-Sep; 2(3): 332-336.
• [14] URL: 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. (Target id: 2863).