Target Information
| Target General Information | Top | |||||
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| Target ID |
T45758
(Former ID: TTDC00188)
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| Target Name |
CD40L receptor (CD40)
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| Synonyms |
Tumor necrosis factor receptor superfamily member 5; TNFRSF5; CDw40; Bp50; B-cell surfaceantigen CD40; B-cell surface antigen CD40
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| Gene Name |
CD40
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 12 Target-related Diseases | + | ||||
| 1 | Lupus erythematosus [ICD-11: 4A40] | |||||
| 2 | Myasthenia gravis [ICD-11: 8C6Y] | |||||
| 3 | Sjogren syndrome [ICD-11: 4A43] | |||||
| 4 | Thyrotoxicosis [ICD-11: 5A02] | |||||
| 5 | Transplant rejection [ICD-11: NE84] | |||||
| 6 | Brain cancer [ICD-11: 2A00] | |||||
| 7 | Crohn disease [ICD-11: DD70] | |||||
| 8 | Melanoma [ICD-11: 2C30] | |||||
| 9 | Ovarian cancer [ICD-11: 2C73] | |||||
| 10 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| 11 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| 12 | Thrombocytopenia [ICD-11: 3B64] | |||||
| Function |
Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion. Receptor for TNFSF5/CD40LG.
Click to Show/Hide
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| BioChemical Class |
Cytokine receptor
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| UniProt ID | ||||||
| Sequence |
MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECL
PCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEACESCV LHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKDLVVQQAGTN KTDVVCGPQDRLRALVVIPIIFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPD DLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T11R4S | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 10 Clinical Trial Drugs | + | ||||
| 1 | APX005M | Drug Info | Phase 2 | Melanoma | [2] | |
| 2 | ASKP-1240 | Drug Info | Phase 2 | Transplant rejection | [3] | |
| 3 | BI 655064 | Drug Info | Phase 2 | Lupus | [4] | |
| 4 | CFZ533 | Drug Info | Phase 2 | Rheumatoid arthritis | [5] | |
| 5 | ABBV-323 | Drug Info | Phase 1 | Crohn disease | [4] | |
| 6 | CDX-1140 | Drug Info | Phase 1 | Solid tumour/cancer | [6] | |
| 7 | CP-870,893 | Drug Info | Phase 1 | Solid tumour/cancer | [7] | |
| 8 | GEN1042 | Drug Info | Phase 1 | Solid tumour/cancer | [8] | |
| 9 | NG-350A | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
| 10 | SL-172154 | Drug Info | Phase 1 | Ovarian cancer | [10] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | HuCD40L | Drug Info | Terminated | Solid tumour/cancer | [11], [12] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 6 Agonist drugs | + | ||||
| 1 | APX005M | Drug Info | [6], [13] | |||
| 2 | CDX-1140 | Drug Info | [15] | |||
| 3 | CP-870,893 | Drug Info | [16] | |||
| 4 | GEN1042 | Drug Info | [17] | |||
| 5 | NG-350A | Drug Info | [18] | |||
| 6 | Human CD40 agonist ligand | Drug Info | [1] | |||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | BI 655064 | Drug Info | [4] | |||
| 2 | CFZ533 | Drug Info | [4], [14] | |||
| 3 | SL-172154 | Drug Info | [19] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | ABBV-323 | Drug Info | [4] | |||
| 2 | Anti-CD40-XTEN | Drug Info | [1] | |||
| Binder | [+] 3 Binder drugs | + | ||||
| 1 | HuCD40L | Drug Info | [20] | |||
| 2 | RhuCD40L | Drug Info | [21] | |||
| 3 | CD154 | Drug Info | [22] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 16 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | NF-kappa B signaling pathway | |||||
| 3 | Cell adhesion molecules (CAMs) | |||||
| 4 | Toll-like receptor signaling pathway | |||||
| 5 | Intestinal immune network for IgA production | |||||
| 6 | Malaria | |||||
| 7 | Toxoplasmosis | |||||
| 8 | HTLV-I infection | |||||
| 9 | Epstein-Barr virus infection | |||||
| 10 | Transcriptional misregulation in cancer | |||||
| 11 | Asthma | |||||
| 12 | Autoimmune thyroid disease | |||||
| 13 | Systemic lupus erythematosus | |||||
| 14 | Allograft rejection | |||||
| 15 | Primary immunodeficiency | |||||
| 16 | Viral myocarditis | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | CD40/CD40L signaling | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | Toll-like receptor signaling pathway | |||||
| 2 | Inflammatory Response Pathway | |||||
| 3 | NLR Proteins | |||||
| 4 | Vitamin D Receptor Pathway | |||||
| 5 | Human Complement System | |||||
| 6 | Allograft Rejection | |||||
| 7 | Regulation of toll-like receptor signaling pathway | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | 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: 1874). | |||||
| REF 2 | ClinicalTrials.gov (NCT04337931) A Study to Evaluate APX005M in Subjects With Unresectable or Metastatic Melanoma. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT01585233) A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | ClinicalTrials.gov (NCT02291029) Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Primary Sj ren's Syndrome. U.S. National Institutes of Health. | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | ClinicalTrials.gov (NCT01103635) Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT04083599) GEN1042 Safety Trial in Subjects With Malignant Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT03852511) First in Human Study of NG-350A (an Oncolytic Adenoviral Vector Which Expresses an Anti-CD40 Antibody) (FORTITUDE). U.S. National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT04406623) Phase 1 Study of SL-172154 (SIRPalpha-Fc-CD40L) in Subjects With Ovarian Cancer. U.S. National Institutes of Health. | |||||
| REF 11 | 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. (Ligand id: 5077). | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008196) | |||||
| REF 13 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 14 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 15 | Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy. Cancer Immunol Immunother. 2019 Feb;68(2):233-245. | |||||
| REF 16 | Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol. 2007 Mar 1;25(7):876-83. | |||||
| REF 17 | Clinical pipeline report, company report or official report of Genmab. | |||||
| REF 18 | Clinical pipeline report, company report or official report of PsiOxus Therapeutics. | |||||
| REF 19 | Clinical pipeline report, company report or official report of Shattuck Labs. | |||||
| REF 20 | Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: a role for interleukin- 16. J Med Primatol. 1999 Aug-Oct;28(4-5):190-4. | |||||
| REF 21 | Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. Cancer Res. 2001 Oct 15;61(20):7556-62. | |||||
| REF 22 | Growth-inhibitory effects of CD40 ligand (CD154) and its endogenous expression in human breast cancer. Clin Cancer Res. 2001 Mar;7(3):691-703. | |||||
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