Target Information
| Target General Information | Top | |||||
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| Target ID |
T06020
(Former ID: TTDR00482)
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| Target Name |
Neonatal Fc receptor (FCGRT)
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| Synonyms |
Neonatal FcR; MHC class I family-like Fc receptor; IgG Fc fragment receptor transporter, alpha chain; FcRn; FCGRT
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| Gene Name |
FCGRT
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Myasthenia gravis [ICD-11: 8C6Y] | |||||
| Function |
Binds to the Fc region of monomericimmunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus.
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MGVPRPQPWALGLLLFLLPGSLGAESHLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLS
YNSLRGEAEPCGAWVWENQVSWYWEKETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCE LGPDNTSVPTAKFALNGEEFMNFDLKQGTWGGDWPEALAISQRWQQQDKAANKELTFLLF SCPHRLREHLERGRGNLEWKEPPSMRLKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGL AAGTGQGDFGPNSDGSFHASSSLTVKSGDEHHYCCIVQHAGLAQPLRVELESPAKSSVLV VGIVIGVLLLTAAAVGGALLWRRMRSGLPAPWISLRGDDTGVLLPTPGEAQDADLKDVNV IPATA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Efgartigimod alfa | Drug Info | Approved | Myasthenia gravis | [2] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | ARGX-113 | Drug Info | Phase 3 | Myasthenia gravis | [3] | |
| 2 | Batoclimab | Drug Info | Phase 3 | Myasthenia gravis | [4] | |
| 3 | Nipocalimab? | Drug Info | Phase 3 | Chronic inflammatory demyelinating polyneuropathy | [5] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Blocker | [+] 1 Blocker drugs | + | ||||
| 1 | Efgartigimod alfa | Drug Info | [2] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | ARGX-113 | Drug Info | [6] | |||
| 2 | Batoclimab | Drug Info | [7] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | SYN-1327 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 1-[7-(3-Fluorophenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]ethanone | Ligand Info | |||||
| Structure Description | Crystal structure of FcRn bound to UCB-84 | PDB:6C98 | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [9] |
| PDB Sequence |
HLSLLYHLTA
13 VSSPAPGTPA23 FWVSGWLGPQ33 QYLSYNSLRG43 EAEPCGAWVW53 ENQVSWYWEK 63 ETTDLRIKEK73 LFLEAFKALG83 GPYTLQGLLG95 CELGPDNTSV105 PTAKFALNGE 115 EFMNFDLKQG125 TWGGDWPEAL135 AISQRWQQQD145 KAANKELTFL155 LFSCPHRLRE 165 HLERGRGNLE175 WKEPPSMRLK185 ARPSSPGFSV195 LTCSAFSFYP205 PELQLRFLRN 215 GLAAGTGQGD225 FGPNSDGSFH235 ASSSLTVKSG245 DEHHYCCIVQ255 HAGLAQPLRV 265 EL
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| Ligand Name: Methyl 7-(3,5-difluorophenyl)-5-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate | Ligand Info | |||||
| Structure Description | Crystal structure of FcRn bound to UCB-303 | PDB:6C99 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [9] |
| PDB Sequence |
HLSLLYHLTA
13 VSSPAPGTPA23 FWVSGWLGPQ33 QYLSYNSLRG43 EAEPCGAWVW53 ENQVSWYWEK 63 ETTDLRIKEK73 LFLEAFKALG83 GKGPYTLQGL93 LGCELGPDNT103 SVPTAKFALN 113 GEEFMNFDLK123 QGTWGGDWPE133 ALAISQRWQQ143 QDKAANKELT153 FLLFSCPHRL 163 REHLERGRGN173 LEWKEPPSMR183 LKARPSSPGF193 SVLTCSAFSF203 YPPELQLRFL 213 RNGLAAGTGQ223 GDFGPNSDGS233 FHASSSLTVK243 SGDEHHYCCI253 VQHAGLAQPL 263 RVELE
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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
Human Tissue Distribution
Biological Network Descriptors
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Butyrophilin subfamily 1 member A1 (BTN1A1) | 22.500 (27/120) | 4.85E-04 |
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.82E-01 | Radiality | 1.30E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 2.80E+01 | Topological coefficient | 5.19E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Structure-activity relationships of a peptide inhibitor of the human FcRn:human IgG interaction. Bioorg Med Chem. 2008 Jun 15;16(12):6394-405. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2021. Application Number: 761195. | |||||
| REF 3 | ClinicalTrials.gov (NCT03770403) A Safety and Tolerability Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness. (ADAPT+). U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT05403541) A Phase 3, Multi-center, Randomized, Quadruple-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Batoclimab as Induction and Maintenance Therapy in Adult Participants With Generalized Myasthenia Gravis (gMG). U.S.National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT05327114) Phase 2/3, Multistage, Multicenter, Randomized, Double-Blind, Placebo-Controlled Parallel Group Withdrawal Study to Evaluate the Efficacy and Safety of Nipocalimab Administered to Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). U.S.National Institutes of Health. | |||||
| REF 6 | Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology. 2019 Jun 4;92(23):e2661-e2673. | |||||
| REF 7 | Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks. Eur J Neurol. 2023 Jan;30(1):195-203. | |||||
| REF 8 | New Therapies for the Treatment of Warm Autoimmune Hemolytic Anemia. Transfus Med Rev. 2022 Oct;36(4):175-180. | |||||
| REF 9 | Insight into small molecule binding to the neonatal Fc receptor by X-ray crystallography and 100 kHz magic-angle-spinning NMR. PLoS Biol. 2018 May 21;16(5):e2006192. | |||||
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