Target Information
Target General Infomation | |||||
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Target ID |
T14755
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Former ID |
TTDR00284
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Target Name |
Tumor necrosis factor ligand superfamily member 5
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Gene Name |
CD40LG
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Synonyms |
CD154 antigen; CD40 ligand; CD40-L; CD40L; T cell antigen Gp39; TNF-related activation protein; TRAP; CD40LG
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Target Type |
Clinical Trial
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Disease | Autoimmune diabetes [ICD10: E08-E13] | ||||
B-cell lymphoma [ICD9: 202.8; ICD10: C85.1] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Chronic lymphocytic leukaemia [ICD10: C91] | |||||
Chronic lymphocytic leukaemia; Mantle cell lymphoma; Small lymphocytic lymphoma [ICD9:200.0, 200.4, 202.0, 202.8, 204.0, 204.1V10.60, 208.9; ICD10: C91, C81-C86, C82, C83.3, C85.7, C91-C95, C91.0, C91.1] | |||||
Lymphoma [ICD9: 202.8, 208.9; ICD10: C81-C86] | |||||
Large B-cell lymphoma; Non-hodgkin's lymphoma [ICD9: 202.8; ICD10: C81-C86] | |||||
Melanoma [ICD9: 172; ICD10: C43] | |||||
Prostate cancer [ICD9: 185; ICD10: C61] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Sjogren's syndrome [ICD9: 710.2; ICD10: M35.0] | |||||
Systemic lupus erythematosus [ICD9: 710; ICD10: M32] | |||||
Thrombocytopenia [ICD9: 287.3, 287.4, 287.5; ICD10: D69.6, P61.0] | |||||
Function |
Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.
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BioChemical Class |
Cytokine: tumor necrosis factor
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UniProt ID | |||||
Sequence |
MIETYNQTSPRSAATGLPISMKIFMYLLTVFLITQMIGSALFAVYLHRRLDKIEDERNLH
EDFVFMKTIQRCNTGERSLSLLNCEEIKSQFEGFVKDIMLNKEETKKENSFEMQKGDQNP QIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSN REASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVN VTDPSQVSHGTGFTSFGLLKL |
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Drugs and Mode of Action | |||||
Drug(s) | IL-2/CD40L-expressing leukemia vaccine | Drug Info | Phase 2 | Chronic lymphocytic leukaemia | [523912] |
ISF35 | Drug Info | Phase 2 | Chronic lymphocytic leukaemia; Mantle cell lymphoma; Small lymphocytic lymphoma | [522732] | |
Lucatumumab | Drug Info | Phase 2 | Lymphoma | [521739] | |
PG-102 | Drug Info | Phase 2 | Autoimmune diabetes | [523012] | |
BI 655064 | Drug Info | Phase 1 | Rheumatoid arthritis | [524565] | |
BPX-101 | Drug Info | Phase 1 | Prostate cancer | [522616] | |
CDP-7657 | Drug Info | Phase 1 | Systemic lupus erythematosus | [522990] | |
Chi Lob 7/4 | Drug Info | Phase 1 | B-cell lymphoma | [523848] | |
CP-870893 | Drug Info | Phase 1 | Cancer | [523006] | |
MEDI4920 | Drug Info | Phase 1 | Sjogren's syndrome | [524779] | |
UltraCD40L | Drug Info | Phase 1 | Systemic lupus erythematosus | [544212] | |
IDEC-131 | Drug Info | Discontinued in Phase 1 | Thrombocytopenia | [546380] | |
Antova | Drug Info | Terminated | Thrombocytopenia | [546796] | |
Dacetuzumab | Drug Info | Terminated | Large B-cell lymphoma; Non-hodgkin's lymphoma | [537129] | |
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Cytokine-cytokine receptor interaction | ||||
NF-kappa B signaling pathway | |||||
Cell adhesion molecules (CAMs) | |||||
T cell receptor signaling pathway | |||||
Intestinal immune network for IgA production | |||||
Malaria | |||||
Toxoplasmosis | |||||
Asthma | |||||
Autoimmune thyroid disease | |||||
Systemic lupus erythematosus | |||||
Allograft rejection | |||||
Primary immunodeficiency | |||||
Viral myocarditis | |||||
NetPath Pathway | IL2 Signaling Pathway | ||||
TNFalpha Signaling Pathway | |||||
TCR Signaling Pathway | |||||
Pathway Interaction Database | IL4-mediated signaling events | ||||
CD40/CD40L signaling | |||||
Calcineurin-regulated NFAT-dependent transcription in lymphocytes | |||||
Beta2 integrin cell surface interactions | |||||
Calcium signaling in the CD4+ TCR pathway | |||||
Reactome | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | ||||
TNFR2 non-canonical NF-kB pathway | |||||
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway | |||||
WikiPathways | Inflammatory Response Pathway | ||||
Allograft Rejection | |||||
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | |||||
References | |||||
Ref 521739 | ClinicalTrials.gov (NCT00231166) Safety, Efficacy, Dose-finding Study of a Monoclonal Antibody in Patients With Multiple Myeloma. U.S. National Institutes of Health. | ||||
Ref 522616 | ClinicalTrials.gov (NCT00868595) MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer. U.S. National Institutes of Health. | ||||
Ref 522732 | ClinicalTrials.gov (NCT00942409) Study of Repeat Intranodal Injection of Memgen's Cancer Vaccine, Ad-ISF35, in Subjects With Non-Hodgkin's Lymphoma (Follicular, Diffuse Large Cell, Mantle Cell, and Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia. U.S. National Institutes of Health. | ||||
Ref 522990 | ClinicalTrials.gov (NCT01093911) Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE). U.S. National Institutes of Health. | ||||
Ref 523006 | ClinicalTrials.gov (NCT01103635) Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma. U.S. National Institutes of Health. | ||||
Ref 523012 | ClinicalTrials.gov (NCT01106703) The Effects of PG102, a Water Soluble Extract From Actinidia Arguta, on Serum Total IgE Levels. U.S. National Institutes of Health. | ||||
Ref 523848 | ClinicalTrials.gov (NCT01561911) A Phase I Study of the Chimeric Anti-CD40 Monoclonal Antibody ChiLob 7/4 to Treat Advanced Malignancies Refractory to Conventional Anti-cancer Treatment. U.S. National Institutes of Health. | ||||
Ref 523912 | ClinicalTrials.gov (NCT01604031) Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide. U.S. National Institutes of Health. | ||||
Ref 524565 | ClinicalTrials.gov (NCT02009761) Multiple Rising Does Study (Subcutaneous Doses) of BI 655064 in Male and Female Patients With Chronic Primary Immune Thrombocytopenic Purpura (ITP).. U.S. National Institutes of Health. | ||||
Ref 524779 | ClinicalTrials.gov (NCT02151110) A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults. U.S. National Institutes of Health. | ||||
Ref 537129 | New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21. | ||||
Ref 544212 | Soluble multi-trimeric TNF superfamily ligand adjuvants enhance immune responses to a HIV-1 Gag DNA vaccine. Vaccine. 2012 January 17; 30(4): 691-702. | ||||
Ref 524779 | ClinicalTrials.gov (NCT02151110) A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults. U.S. National Institutes of Health. | ||||
Ref 525972 | Phase I clinical trial of a monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus. J Rheumatol. 2001 Jan;28(1):95-101. | ||||
Ref 527821 | Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Blood. 2006 Feb15;107(4):1332-41. Epub 2005 Oct 25. | ||||
Ref 531635 | Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. | ||||
Ref 532263 | Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology. 2013 Jan 1;2(1):e23033. | ||||
Ref 532273 | Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL). Biomed Res Int. 2013;2013:976383. | ||||
Ref 532466 | A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin Cancer Res. 2013 Nov 15;19(22):6286-95. | ||||
Ref 533021 | Intratumoral injection of Ad-ISF35 (Chimeric CD154) breaks tolerance and induces lymphoma tumor regression. Hum Gene Ther. 2015 Jan;26(1):14-25. | ||||
Ref 533182 | First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and patients with systemic lupus erythematosus. Lupus. 2015 Sep;24(10):1045-56. | ||||
Ref 533313 | CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study. Arthritis Res Ther. 2015 Sep 3;17:234. | ||||
Ref 544241 | Activation of antigen-exposed iMC-DCs at the ??ight place??and ??ight time??promotes potent anti-tumor immunity. Oncoimmunology. 2012 May 1; 1(3): 362-363. |
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