Target Information

Target General Information

Target ID

T86057 (Former ID: TTDC00243)

Target Name

Urate anion exchanger 1 (URAT1)

Synonyms

UNQ6453/PRO34004; Solute carrier family 22 member 12; Renal-specific transporter; RST; Organic anion transporter 4-like protein; OATL4

Click to Show/Hide

Gene Name

SLC22A12

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

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.

Click to Show/Hide

BioChemical Class

Major facilitator

UniProt ID

S22AC_HUMAN

Sequence

MAFSELLDLVGGLGRFQVLQTMALMVSIMWLCTQSMLENFSAAVPSHRCWAPLLDNSTAQ
ASILGSLSPEALLAISIPPGPNQRPHQCRRFRQPQWQLLDPNATATSWSEADTEPCVDGW
VYDRSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDRFGRRLVLTWSY
LQMAVMGTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLLMEWTAARARPLVMTLNSLG
FSFGHGLTAAVAYGVRDWTLLQLVVSVPFFLCFLYSWWLAESARWLLTTGRLDWGLQELW
RVAAINGKGAVQDTLTPEVLLSAMREELSMGQPPASLGTLLRMPGLRFRTCISTLCWFAF
GFTFFGLALDLQALGSNIFLLQMFIGVVDIPAKMGALLLLSHLGRRPTLAASLLLAGLCI
LANTLVPHEMGALRSALAVLGLGGVGAAFTCITIYSSELFPTVLRMTAVGLGQMAARGGA
ILGPLVRLLGVHGPWLPLLVYGTVPVLSGLAALLLPETQSLPLPDTIQDVQNQAVKKATH
GTLGNSVLKSTQF

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 1 Approved Drugs

Lesinurad

Drug Info

Approved

Hyperuricaemia

[2], [3]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

RDEA-684

Drug Info

Phase 2

Gout

[6]

RDEA3170

Drug Info

Phase 2

Hyperuricaemia

[7]

URC102

Drug Info

Phase 2

Gout

[8]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 2 Modulator drugs

Lesinurad

Drug Info

[1]

RDEA3170

Drug Info

[9]

Inhibitor

[+] 21 Inhibitor drugs

RDEA-684

Drug Info

[1]

URC102

Drug Info

[10]

2-ethyl-3-(4-hydroxy) benzoyl benzofuran derivative 1

Drug Info

[11]

3-benzyloxyphenyloxoacetic acid derivative 1

Drug Info

[11]

Benzene sulfonamide derivative 16

Drug Info

[11]

Benzofurans derivative 1

Drug Info

[11]

Benzoic acid derivative 1

Drug Info

[11]

Cycloalkyl acid derivative 1

Drug Info

[11]

Cycloalkyl acid derivative 2

Drug Info

[11]

Fused heterocyclic compound 12

Drug Info

[11]

Phenylthioacetate derivative 1

Drug Info

[11]

PMID27414413-Compound-Figure6right

Drug Info

[11]

PMID27414413-Compound-Figure8right

Drug Info

[11]

Ring-fused compound 1

Drug Info

[11]

Succinamide derivative 1

Drug Info

[11]

Sulfonamide derivative 10

Drug Info

[11]

Sulfonamide derivative 11

Drug Info

[11]

Tetrazole acetic acid derivative 1

Drug Info

[11]

Tihoacetate derivative 1

Drug Info

[11]

Triazole propanedioic acid derivative 1

Drug Info

[11]

MORIN

Drug Info

[12]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
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

Different Human System Profiles of Target

Top

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Solute carrier family 22 member 25 (SLC22A25)	PF07690	46.741 (251/537)	3.38E-162
Organic anion transporter 7 (SLC22A9)	PF07690	44.585 (247/554)	2.03E-156
Solute carrier family 22 member 7 (SLC22A7)	PF07690	36.447 (199/546)	3.74E-91
Organic cation transporter 3 (OCT3)	PF07690	31.851 (179/562)	3.94E-69

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	2.02E-04
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

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

Top

WikiPathways

[+] 1 WikiPathways

Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

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

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

The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013; 14: 164.

REF 10

Clinical pipeline report, company report or official report of Chugai Pharmaceutical (2013).

REF 11

Urate transporter URAT1 inhibitors: a patent review (2012 - 2015).Expert Opin Ther Pat. 2016 Jul 30:1-10.

REF 12

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.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Yuzong CHEN

Prof. Feng ZHU