Target Information
| Target General Information | Top | |||||
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| Target ID |
T86057
(Former ID: TTDC00243)
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| Target Name |
Urate anion exchanger 1 (URAT1)
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| Synonyms |
UNQ6453/PRO34004; Solute carrier family 22 member 12; Renal-specific transporter; RST; Organic anion transporter 4-like protein; OATL4
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| Gene Name |
SLC22A12
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55] | |||||
| Function |
Regulates blood urate levels. Mediates saturable urate uptake by facilitating the exchange of urate against organic anions. Required for efficient urate re-absorption in the kidney.
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| BioChemical Class |
Major facilitator
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| UniProt ID | ||||||
| Sequence |
MAFSELLDLVGGLGRFQVLQTMALMVSIMWLCTQSMLENFSAAVPSHRCWAPLLDNSTAQ
ASILGSLSPEALLAISIPPGPNQRPHQCRRFRQPQWQLLDPNATATSWSEADTEPCVDGW VYDRSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDRFGRRLVLTWSY LQMAVMGTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLLMEWTAARARPLVMTLNSLG FSFGHGLTAAVAYGVRDWTLLQLVVSVPFFLCFLYSWWLAESARWLLTTGRLDWGLQELW RVAAINGKGAVQDTLTPEVLLSAMREELSMGQPPASLGTLLRMPGLRFRTCISTLCWFAF GFTFFGLALDLQALGSNIFLLQMFIGVVDIPAKMGALLLLSHLGRRPTLAASLLLAGLCI LANTLVPHEMGALRSALAVLGLGGVGAAFTCITIYSSELFPTVLRMTAVGLGQMAARGGA ILGPLVRLLGVHGPWLPLLVYGTVPVLSGLAALLLPETQSLPLPDTIQDVQNQAVKKATH GTLGNSVLKSTQF 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 Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Lesinurad | Drug Info | Approved | Hyperuricaemia | [2], [3] | |
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | Dotinurad | Drug Info | Phase 3 | Gout | [4] | |
| 2 | AR882 | Drug Info | Phase 2 | Gout | [5] | |
| 3 | RDEA-684 | Drug Info | Phase 2 | Gout | [6] | |
| 4 | RDEA3170 | Drug Info | Phase 2 | Hyperuricaemia | [7] | |
| 5 | URC102 | Drug Info | Phase 2 | Gout | [8] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Lesinurad | Drug Info | [1] | |||
| 2 | RDEA3170 | Drug Info | [11] | |||
| Inhibitor | [+] 23 Inhibitor drugs | + | ||||
| 1 | Dotinurad | Drug Info | [9] | |||
| 2 | AR882 | Drug Info | [10] | |||
| 3 | RDEA-684 | Drug Info | [1] | |||
| 4 | URC102 | Drug Info | [12] | |||
| 5 | 2-ethyl-3-(4-hydroxy) benzoyl benzofuran derivative 1 | Drug Info | [13] | |||
| 6 | 3-benzyloxyphenyloxoacetic acid derivative 1 | Drug Info | [13] | |||
| 7 | Benzene sulfonamide derivative 16 | Drug Info | [13] | |||
| 8 | Benzofurans derivative 1 | Drug Info | [13] | |||
| 9 | Benzoic acid derivative 1 | Drug Info | [13] | |||
| 10 | Cycloalkyl acid derivative 1 | Drug Info | [13] | |||
| 11 | Cycloalkyl acid derivative 2 | Drug Info | [13] | |||
| 12 | Fused heterocyclic compound 12 | Drug Info | [13] | |||
| 13 | Phenylthioacetate derivative 1 | Drug Info | [13] | |||
| 14 | PMID27414413-Compound-Figure6right | Drug Info | [13] | |||
| 15 | PMID27414413-Compound-Figure8right | Drug Info | [13] | |||
| 16 | Ring-fused compound 1 | Drug Info | [13] | |||
| 17 | Succinamide derivative 1 | Drug Info | [13] | |||
| 18 | Sulfonamide derivative 10 | Drug Info | [13] | |||
| 19 | Sulfonamide derivative 11 | Drug Info | [13] | |||
| 20 | Tetrazole acetic acid derivative 1 | Drug Info | [13] | |||
| 21 | Tihoacetate derivative 1 | Drug Info | [13] | |||
| 22 | Triazole propanedioic acid derivative 1 | Drug Info | [13] | |||
| 23 | MORIN | Drug Info | [14] | |||
| 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 | 1.62E-01 | Radiality | 1.24E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 3.00E+00 | Topological coefficient | 5.00E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds | |||||
| 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: 1031). | |||||
| 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: 7673). | |||||
| REF 3 | ClinicalTrials.gov (NCT01493531) Combining Lesinurad With Allopurinol in Inadequate Responders. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT05007392) A Randomized, Multicenter, Double-Blind, Superiority Study of Dotinurad (4 mg) and Febuxostat (40 mg) for the Treatment of Subjects With Gout. U.S.National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT04155918) A Phase 2a, Open-Label Study to Evaluate the Safety and Efficacy of AR882 Administered Alone or in Combination With Febuxostat or Allopurinol in Gout Patients. U.S.National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT01927198) RDEA3170 Monotherapy in Subjects With Gout. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT02078219) Phase II Dose Finding Study of RDEA3170 Versus Placebo in Japanese Patients With Gout or Asymptomatic Hyperuricemia. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT02290210) Phase 2 Study of URC102 to Assess the Efficacy and Safety in Gout Patients. U.S. National Institutes of Health. | |||||
| REF 9 | Dotinurad: a novel selective urate reabsorption inhibitor for the treatment of hyperuricemia and gout. Expert Opin Pharmacother. 2021 Aug;22(11):1397-1406. | |||||
| REF 10 | Clinical pipeline report, company report or official report of Arthrosi Therapeutics | |||||
| REF 11 | The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013; 14: 164. | |||||
| REF 12 | Clinical pipeline report, company report or official report of Chugai Pharmaceutical (2013). | |||||
| REF 13 | Urate transporter URAT1 inhibitors: a patent review (2012 - 2015).Expert Opin Ther Pat. 2016 Jul 30:1-10. | |||||
| REF 14 | Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) express... Drug Metab Dispos. 2007 Jun;35(6):981-6. | |||||
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