Target Information
Target General Information | Top | |||||
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Target ID |
T28993
(Former ID: TTDI02286)
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Target Name |
Iduronate 2-sulfatase (IDS)
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Synonyms |
Idursulfase; Iduronate 2sulfatase 14 kDa chain; IDS; AlphaLiduronate sulfate sulfatase
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Gene Name |
IDS
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Lysosomal disease [ICD-11: 5C56] | |||||
2 | Male infertility [ICD-11: GB04] | |||||
Function |
Required for the lysosomal degradation ofheparan sulfate and dermatan sulfate.
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BioChemical Class |
Sulfuric ester hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.1.6.13
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Sequence |
MPPPRTGRGLLWLGLVLSSVCVALGSETQANSTTDALNVLLIIVDDLRPSLGCYGDKLVR
SPNIDQLASHSLLFQNAFAQQAVCAPSRVSFLTGRRPDTTRLYDFNSYWRVHAGNFSTIP QYFKENGYVTMSVGKVFHPGISSNHTDDSPYSWSFPPYHPSSEKYENTKTCRGPDGELHA NLLCPVDVLDVPEGTLPDKQSTEQAIQLLEKMKTSASPFFLAVGYHKPHIPFRYPKEFQK LYPLENITLAPDPEVPDGLPPVAYNPWMDIRQREDVQALNISVPYGPIPVDFQRKIRQSY FASVSYLDTQVGRLLSALDDLQLANSTIIAFTSDHGWALGEHGEWAKYSNFDVATHVPLI FYVPGRTASLPEAGEKLFPYLDPFDSASQLMEPGRQSMDLVELVSLFPTLAGLAGLQVPP RCPVPSFHVELCREGKNLLKHFRFRDLEEDPYLPGNPRELIAYSQYPRPSDIPQWNSDKP SLKDIKIMGYSIRTIDYRYTVWVGFNPDEFLANFSDIHAGELYFVDSDPLQDHNMYNDSQ GGDLFQLLMP 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 | Idursulfase | Drug Info | Approved | Infertility | [1], [2], [3] | |
Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
1 | Recombinant human iduronate-2-sulfatase | Drug Info | Phase 3 | Hunter syndrome | [4] | |
2 | DNL310 | Drug Info | Phase 2/3 | Mucopolysaccharidosis II | [5] | |
3 | RGX-121 | Drug Info | Phase 1/2 | Mucopolysaccharidosis | [6] | |
4 | SB-913 | Drug Info | Phase 1/2 | Mucopolysaccharidosis | [7] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | Idursulfase | Drug Info | [1], [2] | |||
2 | Recombinant human iduronate-2-sulfatase | Drug Info | [8] | |||
Replacement | [+] 3 Replacement drugs | + | ||||
1 | DNL310 | Drug Info | [9] | |||
2 | RGX-121 | Drug Info | [10] | |||
3 | SB-913 | Drug Info | [7] |
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).
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).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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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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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Glycosaminoglycan degradation | hsa00531 | Affiliated Target |
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Class: Metabolism => Glycan biosynthesis and metabolism | Pathway Hierarchy | ||
Lysosome | hsa04142 | Affiliated Target |
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Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy |
Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 9.02E-02 | Radiality | 8.06E+00 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 3.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 16 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 1 BioCyc Pathways | + | ||||
1 | Dermatan sulfate degradation (metazoa) | |||||
KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | Glycosaminoglycan degradation | |||||
2 | Metabolic pathways | |||||
3 | Lysosome | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | HS-GAG degradation | |||||
2 | CS/DS degradation | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Glycosaminoglycan metabolism |
References | Top | |||||
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REF 1 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. | |||||
REF 2 | A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 4 | ClinicalTrials.gov (NCT01645189) Safety and Efficacy of Hunterase. U.S. National Institutes of Health. | |||||
REF 5 | ClinicalTrials.gov (NCT05371613) A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of DNL310 vs Idursulfase in Pediatric Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II. U.S.National Institutes of Health. | |||||
REF 6 | ClinicalTrials.gov (NCT04571970) RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome). U.S. National Institutes of Health. | |||||
REF 7 | ClinicalTrials.gov (NCT03041324) Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II. U.S. National Institutes of Health. | |||||
REF 8 | The effect of recombinant human iduronate-2-sulfatase (Idursulfase) on growth in young patients with mucopolysaccharidosis type II. PLoS One. 2014 Jan 13;9(1):e85074. | |||||
REF 9 | Clinical pipeline report, company report or official report of Denali | |||||
REF 10 | Clinical pipeline report, company report or official report of REGENXBIO. |
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