Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA592U)

• DTT 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
• Gene Name: SLC22A12
• DTT Type: Successful target; [1]
• Related Disease: Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55]
• BioChemical Class: Major facilitator
• UniProt ID: S22AC_HUMAN
• TTD ID: T86057
• Sequence:
  MAFSELLDLVGGLGRFQVLQTMALMVSIMWLCTQSMLENFSAAVPSHRCWAPLLDNSTAQ
  ASILGSLSPEALLAISIPPGPNQRPHQCRRFRQPQWQLLDPNATATSWSEADTEPCVDGW
  VYDRSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDRFGRRLVLTWSY
  LQMAVMGTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLLMEWTAARARPLVMTLNSLG
  FSFGHGLTAAVAYGVRDWTLLQLVVSVPFFLCFLYSWWLAESARWLLTTGRLDWGLQELW
  RVAAINGKGAVQDTLTPEVLLSAMREELSMGQPPASLGTLLRMPGLRFRTCISTLCWFAF
  GFTFFGLALDLQALGSNIFLLQMFIGVVDIPAKMGALLLLSHLGRRPTLAASLLLAGLCI
  LANTLVPHEMGALRSALAVLGLGGVGAAFTCITIYSSELFPTVLRMTAVGLGQMAARGGA
  ILGPLVRLLGVHGPWLPLLVYGTVPVLSGLAALLLPETQSLPLPDTIQDVQNQAVKKATH
  GTLGNSVLKSTQF
• 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.
• Reactome Pathway:
  Defective SLC22A12 causes renal hypouricemia 1 (RHUC1) (R-HSA-5619071)
  Organic anion transport (R-HSA-561048)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lesinurad	DMUR64T	Hyperuricaemia	5C55.Y	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RDEA-684	DMNWYHD	Gout	FA25	Phase 2	[1]
RDEA3170	DM1TKG4	Hyperuricaemia	5C55.Y	Phase 2	[2]
URC102	DMY89BN	Gout	FA25	Phase 2	[3]

18 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-ethyl-3-(4-hydroxy) benzoyl benzofuran derivative 1	DMHYIAV	N. A.	N. A.	Patented	[4]
3-benzyloxyphenyloxoacetic acid derivative 1	DMB6M3Y	N. A.	N. A.	Patented	[4]
Benzene sulfonamide derivative 16	DMATBZW	N. A.	N. A.	Patented	[4]
Benzofurans derivative 1	DM4198Z	N. A.	N. A.	Patented	[4]
Benzoic acid derivative 1	DM5ZKR2	N. A.	N. A.	Patented	[4]
Cycloalkyl acid derivative 1	DMXMGSP	N. A.	N. A.	Patented	[4]
Cycloalkyl acid derivative 2	DM09LY3	N. A.	N. A.	Patented	[4]
Fused heterocyclic compound 12	DMSYD6Z	N. A.	N. A.	Patented	[4]
Phenylthioacetate derivative 1	DMTHXUC	N. A.	N. A.	Patented	[4]
PMID27414413-Compound-Figure6right	DMUG9X0	N. A.	N. A.	Patented	[4]
PMID27414413-Compound-Figure8right	DMTZNSM	N. A.	N. A.	Patented	[4]
Ring-fused compound 1	DMUB7RV	N. A.	N. A.	Patented	[4]
Succinamide derivative 1	DMTXDSG	N. A.	N. A.	Patented	[4]
Sulfonamide derivative 10	DMA32GJ	N. A.	N. A.	Patented	[4]
Sulfonamide derivative 11	DMJBR86	N. A.	N. A.	Patented	[4]
Tetrazole acetic acid derivative 1	DM52683	N. A.	N. A.	Patented	[4]
Tihoacetate derivative 1	DM6QHO0	N. A.	N. A.	Patented	[4]
Triazole propanedioic acid derivative 1	DM8LFGS	N. A.	N. A.	Patented	[4]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Morin	DM2OGZ5	Discovery agent	N.A.	Investigative	[5]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Urate anion exchanger 1 (SLC22A12) DTP Info
• Gene Name: SLC22A12

1 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Oxypurinol	DMURH4X	Heart failure	BD10-BD13	Phase 2/3	[6]

2 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Orotate	DMMB29S	Discovery agent	N.A.	Investigative	[7]
Uric acid	DMA1MKT	Discovery agent	N.A.	Investigative	[8]

References

• [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).
• [2] The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013; 14: 164.
• [3] Clinical pipeline report, company report or official report of Chugai Pharmaceutical (2013).
• [4] Urate transporter URAT1 inhibitors: a patent review (2012 - 2015).Expert Opin Ther Pat. 2016 Jul 30:1-10.
• [5] 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.
• [6] Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos. 2005 Dec;33(12):1791-5.
• [7] Human urate transporter 1 (hURAT1) mediates the transport of orotate. J Physiol Sci. 2011 May;61(3):253-7.
• [8] Concentration-dependent mode of interaction of angiotensin II receptor blockers with uric acid transporter. J Pharmacol Exp Ther. 2007 Jan;320(1):211-7.