Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN2JFW)

• DTT Name: T-cell surface glycoprotein CD4 (CD4)
• Synonyms: T-cell surface antigen T4/Leu-3
• Gene Name: CD4
• DTT Type: Successful target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: CD4_HUMAN
• TTD ID: T10191
• Sequence:
  MNRGVPFRHLLLVLQLALLPAATQGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIK
  ILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQL
  LVFGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGGKTLSVSQLELQDSG
  TWTCTVLQNQKKVEFKIDIVVLAFQKASSIVYKKEGEQVEFSFPLAFTVEKLTGSGELWW
  QAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLA
  LEAKTGKLHQEVNLVVMRATQLQKNLTCEVWGPTSPKLMLSLKLENKEAKVSKREKAVWV
  LNPEAGMWQCLLSDSGQVLLESNIKVLPTWSTPVQPMALIVLGGVAGLLLFIGLGIFFCV
  RCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI
• Function: In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  Antigen processing and presentation (hsa04612)
  Hematopoietic cell lineage (hsa04640)
  T cell receptor signaling pathway (hsa04660)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)
  Translocation of ZAP-70 to Immunological synapse (R-HSA-202430)
  Generation of second messenger molecules (R-HSA-202433)
  PD-1 signaling (R-HSA-389948)
  Binding and entry of HIV virion (R-HSA-173107)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibalizumab	DMV67QO	Human immunodeficiency virus infection	1C62	Approved	[1]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Magrolimab	DMVXUR0	Acute myeloid leukaemia	2A60	Phase 3	[2]
TNX-355	DMYA41S	Human immunodeficiency virus infection	1C62	Phase 3	[3]
Zanolimumab	DMKB4ZY	Lymphoma	2A80-2A86	Phase 3	[4]
BT-061	DM2LZIY	Asthma	CA23	Phase 2	[5]
Fluoropeptide vaccine	DMCEUOH	Influenza virus infection	1E30-1E32	Phase 2	[6]
CD4CAR	DM09SW6	T-cell leukaemia	2A90	Phase 1	[7]
Combinectin	DMTLP1N	Human immunodeficiency virus infection	1C62	Phase 1	[8]
LIPO-4	DMJRALD	Human immunodeficiency virus infection	1C62	Phase 1	[9]
TMB-365	DMH3E5C	Human immunodeficiency virus-1 infection	1C62	Phase 1	[10]
VRC07-523LS	DM0S9OT	Human immunodeficiency virus-1 infection	1C62	Phase 1	[11]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IDEC-151	DMILUHA	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[12]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CEL-1000	DMRYX1P	Solid tumour/cancer	2A00-2F9Z	Investigative	[13]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	2.23E-07	-0.23	-0.79
Rheumatoid arthritis	FA20	Synovial tissue	9.36E-04	0.67	2.62

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] Current and emerging strategies for management of myelodysplastic syndromes. Blood Rev. 2021 Jul;48:100791.
• [3] Progress in targeting HIV-1 entry. Drug Discov Today. 2005 Aug 15;10(16):1085-94.
• [4] Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma. Blood. 2007 Jun 1;109(11):4655-62.
• [5] Tregalizumab (BT-061) increases regulatory T cell function. Boosting regulatory T-cell function with the humanized CD4-specific humanized monoclonal antibody Tregalizumab (BT-061). Immunol Cell Biol.2015 Apr;93(4):321-2.
• [6] A novel peptide-based pan-influenza A vaccine: a double blind, randomised clinical trial of immunogenicity and safety. Vaccine. 2015 Jan 3;33(2):396-402.
• [7] Clinical pipeline report, company report or official report of iCell Gene Therapeutics.
• [8] Clinical pipeline report, company report or official report of ViiV Healthcare.
• [9] Long-term CD4(+) and CD8(+) T-cell responses induced in HIV-uninfected volunteers following intradermal or intramuscular administration of an HIV-lipopeptide vaccine (ANRS VAC16). Vaccine. 2013 Sep 13;31(40):4406-15.
• [10] Clinical pipeline report, company report or official report of TaiMed Biologics.
• [11] Clinical pipeline report, company report or official report of TaiMed Biologics.
• [12] Comparative pharmacodynamics of keliximab and clenoliximab in transgenic mice bearing human CD4. J Pharmacol Exp Ther. 2000 Apr;293(1):33-41.
• [13] A small peptide (CEL-1000) derived from the beta-chain of the human major histocompatibility complex class II molecule induces complete protection against malaria in an antigen-independent manner. Antimicrob Agents Chemother. 2004 Jul;48(7):2455-63.