Target Information
| Target General Information | Top | |||||
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| Target ID |
T15000
(Former ID: TTDC00259)
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| Target Name |
Cytotoxic T-lymphocyte protein 4 (CTLA-4)
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| Synonyms |
Cytotoxic T-lymphocyte-associated antigen 4; CTLA-4; CD152
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| Gene Name |
CTLA4
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Melanoma [ICD-11: 2C30] | |||||
| Function |
Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.
Click to Show/Hide
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEY
ASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLR AMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVSSGLFFYSFL LTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T75U40 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Ipilimumab | Drug Info | Approved | Melanoma | [1], [2], [3] | |
| Clinical Trial Drug(s) | [+] 17 Clinical Trial Drugs | + | ||||
| 1 | KN046 | Drug Info | Phase 3 | Non-small-cell lung cancer | [4] | |
| 2 | Tremelimumab | Drug Info | Phase 3 | Solid tumour/cancer | [5], [6] | |
| 3 | AK104 | Drug Info | Phase 2 | Cervical cancer | [7] | |
| 4 | AGEN1884 | Drug Info | Phase 1/2 | Cervical cancer | [8] | |
| 5 | BMS-986288 | Drug Info | Phase 1/2 | Solid tumour/cancer | [9] | |
| 6 | MK-1308 | Drug Info | Phase 1/2 | Solid tumour/cancer | [10] | |
| 7 | ADG116 | Drug Info | Phase 1 | Solid tumour/cancer | [11] | |
| 8 | AGEN1181 | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
| 9 | ALPN-202 | Drug Info | Phase 1 | Solid tumour/cancer | [13] | |
| 10 | BMS-986249 | Drug Info | Phase 1 | Solid tumour/cancer | [8] | |
| 11 | MEDI5752 | Drug Info | Phase 1 | Solid tumour/cancer | [14] | |
| 12 | MGD019 | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
| 13 | ONC-392 | Drug Info | Phase 1 | Non-small-cell lung cancer | [16] | |
| 14 | SI-B003 | Drug Info | Phase 1 | Solid tumour/cancer | [17] | |
| 15 | TRemelimumab + MEDI0562 | Drug Info | Phase 1 | Solid tumour/cancer | [18] | |
| 16 | XmAb20717 | Drug Info | Phase 1 | Solid tumour/cancer | [19] | |
| 17 | XmAb22841 | Drug Info | Phase 1 | Solid tumour/cancer | [20] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Inhibitor | [+] 12 Inhibitor drugs | + | ||||
| 1 | KN046 | Drug Info | [21] | |||
| 2 | AK104 | Drug Info | [23] | |||
| 3 | BMS-986288 | Drug Info | [24] | |||
| 4 | MK-1308 | Drug Info | [25] | |||
| 5 | ADG116 | Drug Info | [26] | |||
| 6 | AGEN1181 | Drug Info | [27] | |||
| 7 | ALPN-202 | Drug Info | [28] | |||
| 8 | MEDI5752 | Drug Info | [29] | |||
| 9 | MGD019 | Drug Info | [30] | |||
| 10 | ONC-392 | Drug Info | [31] | |||
| 11 | Alpha-D-Mannose | Drug Info | [35] | |||
| 12 | Fucose | Drug Info | [35] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | Tremelimumab | Drug Info | [22] | |||
| 2 | Concatameric CTLA4Ig | Drug Info | [22] | |||
| 3 | CTLA-4-XTEN | Drug Info | [22] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | AGEN1884 | Drug Info | [8], [18] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | TRemelimumab + MEDI0562 | Drug Info | [18] | |||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Cell adhesion molecules (CAMs) | |||||
| 2 | T cell receptor signaling pathway | |||||
| 3 | Autoimmune thyroid disease | |||||
| 4 | Rheumatoid arthritis | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Calcineurin-regulated NFAT-dependent transcription in lymphocytes | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | CTLA4 inhibitory signaling | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Vitamin D Receptor Pathway | |||||
| 2 | T-Cell Receptor and Co-stimulatory Signaling | |||||
| 3 | Allograft Rejection | |||||
| 4 | Costimulation by the CD28 family | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5. | |||||
| REF 2 | 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: 6888). | |||||
| REF 3 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
| REF 4 | ClinicalTrials.gov (NCT04474119) KN046 in Subjects With Advanced Squamous Non-small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 5 | 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: 8462). | |||||
| REF 6 | ClinicalTrials.gov (NCT02551159) Phase III Open Label First Line Therapy Study of MEDI 4736 With or Without Tremelimumab Versus Standard of Care (SOC) in SCCHN. | |||||
| REF 7 | ClinicalTrials.gov (NCT04380805) A Study of AK104, a PD-1/CTLA-4 Bispecific Antibody in Subjects With Recurrent/Metastatic Cervical Cancer. U.S. National Institutes of Health. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | ClinicalTrials.gov (NCT03994601) An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers. U.S. National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT03179436) Study of Quavonlimab (MK-1308) in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-1308-001). U.S. National Institutes of Health. | |||||
| REF 11 | ClinicalTrials.gov (NCT04501276) ADG116 in Patients With Advanced/Metastatic Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT03860272) Fc-Engineered Anti-CTLA-4 Monoclonal Antibody in Advanced Cancer. U.S. National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT04186637) An Open-label Study of ALPN-202 in Subjects With Advanced Malignancies (NEON-1). U.S. National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT03530397) A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT03761017) MGD019 DART Protein in Unresectable/Metastatic Cancer. U.S. National Institutes of Health. | |||||
| REF 16 | ClinicalTrials.gov (NCT04140526) Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC (PRESERVE-001). U.S. National Institutes of Health. | |||||
| REF 17 | ClinicalTrials.gov (NCT04606472) A Study of SI-B003, a PD-1/CTLA-4 Bispecific Antibody, in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 18 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 19 | Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway.J Med Chem. 2019 Feb 28;62(4):1715-1730. | |||||
| REF 20 | ClinicalTrials.gov (NCT03849469) A Study of XmAb22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors (DUET-4). U.S. National Institutes of Health. | |||||
| REF 21 | Clinical pipeline report, company report or official report of Alphamab Oncology. | |||||
| REF 22 | 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: 2743). | |||||
| REF 23 | Clinical pipeline report, company report or official report of Akeso Biopharma. | |||||
| REF 24 | Clinical pipeline report, company report or official report of CytomX Therapeutics. | |||||
| REF 25 | Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer. Ann Oncol. 2021 Mar;32(3):395-403. | |||||
| REF 26 | Clinical pipeline report, company report or official report of Adagene. | |||||
| REF 27 | Clinical pipeline report, company report or official report of Agenus. | |||||
| REF 28 | Clinical pipeline report, company report or official report of Alpine Immune Sciences. | |||||
| REF 29 | Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity. Cancer Discov. 2021 May;11(5):1008-1010. | |||||
| REF 30 | Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. Cell Rep Med. 2020 Dec 22;1(9):100163. | |||||
| REF 31 | Clinical pipeline report, company report or official report of OncoImmune. | |||||
| REF 32 | Clinical pipeline report, company report or official report of SystImmune. | |||||
| REF 33 | Clinical pipeline report, company report or official report of Xencor. | |||||
| REF 34 | Clinical pipeline report, company report or official report of Xencor. | |||||
| REF 35 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 36 | Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60. | |||||
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