Target Information
| Target General Information | Top | |||||
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| Target ID |
T94718
(Former ID: TTDNC00414)
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| Target Name |
Lymphocyte activation gene 3 protein (LAG3)
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| Synonyms |
Protein FDC; LAG-3; FDC; CD223
Click to Show/Hide
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| Gene Name |
LAG3
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Melanoma [ICD-11: 2C30] | |||||
| 2 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
| Function |
Delivers inhibitory signals upon binding to ligands, such as FGL1. FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function. Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1. Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells. Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function. Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation. Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear. Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells.
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MWEAQFLGLLFLQPLWVAPVKPLQPGAEVPVVWAQEGAPAQLPCSPTIPLQDLSLLRRAG
VTWQHQPDSGPPAAAPGHPLAPGPHPAAPSSWGPRPRRYTVLSVGPGGLRSGRLPLQPRV QLDERGRQRGDFSLWLRPARRADAGEYRAAVHLRDRALSCRLRLRLGQASMTASPPGSLR ASDWVILNCSFSRPDRPASVHWFRNRGQGRVPVRESPHHHLAESFLFLPQVSPMDSGPWG CILTYRDGFNVSIMYNLTVLGLEPPTPLTVYAGAGSRVGLPCRLPAGVGTRSFLTAKWTP PGGGPDLLVTGDNGDFTLRLEDVSQAQAGTYTCHIHLQEQQLNATVTLAIITVTPKSFGS PGSLGKLLCEVTPVSGQERFVWSSLDTPSQRSFSGPWLEAQEAQLLSQPWQCQLYQGERL LGAAVYFTELSSPGAQRSGRAPGALPAGHLLLFLILGVLSLLLLVTGAFGFHLWRRQWRP RRFSALEQGIHPPQAQSKIEELEQEPEPEPEPEPEPEPEPEPEQL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved | [+] 1 | + | ||||
| 1 | Relatlimab | Drug Info | Approved | Melanoma | [1] | |
| Clinical Trial Drug(s) | [+] 15 Clinical Trial Drugs | + | ||||
| 1 | Anti-LAG3 | Drug Info | Phase 2 | Gastric adenocarcinoma | [2] | |
| 2 | BMS-986016 | Drug Info | Phase 1/2 | Hematologic tumour | [3] | |
| 3 | Favezelimab | Drug Info | Phase 1/2 | Non-hodgkin lymphoma | [4] | |
| 4 | IMP-321 | Drug Info | Phase 1/2 | Allergy | [5] | |
| 5 | A289 | Drug Info | Phase 1 | Aggressive cancer | [6] | |
| 6 | ADPT01 | Drug Info | Phase 1 | Breast cancer | [7] | |
| 7 | FS118 | Drug Info | Phase 1 | Advanced malignancy | [8] | |
| 8 | GSK2831781 | Drug Info | Phase 1 | Autoimmune disease | [9] | |
| 9 | GSK4074386 | Drug Info | Phase 1 | Solid tumour/cancer | [10] | |
| 10 | IMP-701 | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
| 11 | INCAGN2385 | Drug Info | Phase 1 | Melanoma | [11] | |
| 12 | MK-4280 | Drug Info | Phase 1 | Solid tumour/cancer | [8] | |
| 13 | RG6139 | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
| 14 | Sym022 | Drug Info | Phase 1 | Lymphoma | [13] | |
| 15 | XmAb22841 | Drug Info | Phase 1 | Solid tumour/cancer | [14] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Inhibitor | [+] 8 Inhibitor drugs | + | ||||
| 1 | Anti-LAG3 | Drug Info | [2] | |||
| 2 | ADPT01 | Drug Info | [7] | |||
| 3 | GSK2831781 | Drug Info | [20] | |||
| 4 | GSK4074386 | Drug Info | [10] | |||
| 5 | INCAGN2385 | Drug Info | [21] | |||
| 6 | MK-4280 | Drug Info | [22] | |||
| 7 | RG6139 | Drug Info | [23] | |||
| 8 | Sym022 | Drug Info | [24] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | BMS-986016 | Drug Info | [15] | |||
| 2 | Concatameric LAG3Ig | Drug Info | [18] | |||
| 3 | IMP-731 | Drug Info | [18] | |||
| Immunomodulator | [+] 1 Immunomodulator drugs | + | ||||
| 1 | IMP-321 | Drug Info | [17], [18] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Biological Network Descriptors
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| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 2.02E-04 |
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| Closeness centrality | 1.95E-01 | Radiality | 1.33E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.15E+01 | Topological coefficient | 5.00E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 761234 | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | ClinicalTrials.gov (NCT02061761) Safety Study of Anti-LAG-3 in CLL, HL, NHL and MM. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT03598608) A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies. U.S.National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01308294) Immunotherapy of HLA-A2 Positive Stage II-IV Melanoma Patients. U.S. National Institutes of Health. | |||||
| REF 6 | Clinical pipeline report, company report or official report of Klus Pharma | |||||
| REF 7 | Clinical pipeline report, company report or official report of Novartis. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 10 | Clinical pipeline report, company report or official report of GlaxoSmithKline. | |||||
| REF 11 | ClinicalTrials.gov (NCT04370704) Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT04140500) Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT03489369) Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas. U.S. National Institutes of Health. | |||||
| REF 14 | 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 15 | Nivolumab in NSCLC: latest evidence and clinical potential. Ther Adv Med Oncol. 2015 March; 7(2): 85-96. | |||||
| REF 16 | A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. ESMO Open. 2022 Dec;7(6):100639. | |||||
| REF 17 | A soluble form of lymphocyte activation gene-3 (IMP321) induces activation of a large range of human effector cytotoxic cells. J Immunol. 2007 Sep 15;179(6):4202-11. | |||||
| REF 18 | IMP321 (sLAG-3), an immunopotentiator for T cell responses against a HBsAg antigen in healthy adults: a single blind randomised controlled phase I study. J Immune Based Ther Vaccines. 2007 Mar 29;5:5. | |||||
| 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 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 21 | Clinical pipeline report, company report or official report of Agenus. | |||||
| REF 22 | Establishment of engineered cell-based assays mediating LAG3 and PD1 immune suppression enables potency measurement of blocking antibodies and assessment of signal transduction. J Immunol Methods. 2018 May;456:7-14. | |||||
| REF 23 | Clinical pipeline report, company report or official report of Genentech. | |||||
| REF 24 | Clinical pipeline report, company report or official report of Symphogen. | |||||
| REF 25 | Clinical pipeline report, company report or official report of Xencor. | |||||
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