Target Information

Target General Infomation
Target ID
T54771
Former ID
TTDC00260
Target Name
Sodium/glucose cotransporter 1
Gene Name
SLC5A1
Synonyms
High affinity sodium-glucose cotransporter; Na(+)/glucose cotransporter 1; Solute carrier family 5 member 1; SLC5A1
Target Type
Clinical Trial
Disease Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Function
Actively transports glucose into cells by Na(+) cotransport with a Na(+) to glucose coupling ratio of 2:1. Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na(+)/glucose cotransporter arranged in series along kidney proximal tubules.
BioChemical Class
Solute:sodium symporter
Target Validation
T54771
UniProt ID
P13866
Sequence
MDSSTWSPKTTAVTRPVETHELIRNAADISIIVIYFVVVMAVGLWAMFSTNRGTVGGFFL
AGRSMVWWPIGASLFASNIGSGHFVGLAGTGAASGIAIGGFEWNALVLVVVLGWLFVPIY
IKAGVVTMPEYLRKRFGGQRIQVYLSLLSLLLYIFTKISADIFSGAIFINLALGLNLYLA
IFLLLAITALYTITGGLAAVIYTDTLQTVIMLVGSLILTGFAFHEVGGYDAFMEKYMKAI
PTIVSDGNTTFQEKCYTPRADSFHIFRDPLTGDLPWPGFIFGMSILTLWYWCTDQVIVQR
CLSAKNMSHVKGGCILCGYLKLMPMFIMVMPGMISRILYTEKIACVVPSECEKYCGTKVG
CTNIAYPTLVVELMPNGLRGLMLSVMLASLMSSLTSIFNSASTLFTMDIYAKVRKRASEK
ELMIAGRLFILVLIGISIAWVPIVQSAQSGQLFDYIQSITSYLGPPIAAVFLLAIFWKRV
NEPGAFWGLILGLLIGISRMITEFAYGTGSCMEPSNCPTIICGVHYLYFAIILFAISFIT
IVVISLLTKPIPDVHLYRLCWSLRNSKEERIDLDAEEENIQEGPKETIEIETQVPEKKKG
IFRRAYDLFCGLEQHGAPKMTEEEEKAMKMKMTDTSEKPLWRTVLNVNGIILVTVAVFCH
AYFA
Drugs and Mode of Action
Drug(s) LIK-066 Drug Info Phase 2 Type 2 diabetes [524252]
LX-4211 Drug Info Phase 2 Type 2 diabetes [524151], [543064]
1614235 + 2330672 Drug Info Phase 1 Type 2 diabetes [549464]
GSK1614235 Drug Info Phase 1 Type 2 diabetes [523921]
T-1095 Drug Info Discontinued in Phase 2 Diabetes [546954]
Inhibitor 10-methoxy-N(1)-methylburnamine-17-O-veratrate Drug Info [530756]
Acerogenin A Drug Info [530603]
ACEROGENIN B Drug Info [530603]
Alstiphyllanine D Drug Info [530756]
Alstiphyllanine E Drug Info [530756]
Alstiphyllanine F Drug Info [530756]
Burnamine-17-O-3',4',5'-trimethoxybenzoate Drug Info [530756]
KURAIDIN Drug Info [528742]
KURARINONE Drug Info [528742]
Kushenol N Drug Info [528742]
LIK-066 Drug Info [543973]
O-spiroketal glucoside Drug Info [530988]
Phlorizin Drug Info [533444]
QCP Drug Info [528982]
QCPac Drug Info [528982]
QNEQCPQVSac Drug Info [528982]
QSPac Drug Info [528982]
sergliflozin Drug Info [528482]
Sophoraflavanone G Drug Info [528742]
Modulator 1614235 + 2330672 Drug Info [543973]
LX-4211 Drug Info [531953]
T-1095 Drug Info [525583]
Blocker GSK1614235 Drug Info [550963]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Carbohydrate digestion and absorption
Bile secretion
Mineral absorption
PathWhiz Pathway Lactose Degradation
Trehalose Degradation
Reactome Hexose transport
Na+-dependent glucose transporters
Inositol transporters
WikiPathways NRF2 pathway
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds
Metabolism of carbohydrates
References
Ref 523921ClinicalTrials.gov (NCT01607385) A Study to Evaluate the Safety, Tolerability, Pharmacokinetic a Single Day of Dosing With GSK1614235.. U.S. National Institutes of Health.
Ref 524151ClinicalTrials.gov (NCT01742208) Safety and Efficacy of LX4211 in Patients With Inadequately Controlled Type 1 Diabetes Mellitus. U.S. National Institutes of Health.
Ref 524252ClinicalTrials.gov (NCT01824264) Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes. U.S. National Institutes of Health.
Ref 543064(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: 8312).
Ref 546954Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011538)
Ref 549464Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037723)
Ref 525583T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
Ref 528482Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther. 2007 Jan;320(1):323-30. Epub 2006 Oct 18.
Ref 528742Bioorg Med Chem. 2007 May 15;15(10):3445-9. Epub 2007 Mar 12.Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens.
Ref 528982J Biol Chem. 2007 Sep 28;282(39):28501-13. Epub 2007 Aug 8.Tripeptides of RS1 (RSC1A1) inhibit a monosaccharide-dependent exocytotic pathway of Na+-D-glucose cotransporter SGLT1 with high affinity.
Ref 530603Bioorg Med Chem Lett. 2010 Feb 1;20(3):1070-4. Epub 2009 Dec 11.Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense.
Ref 530756Bioorg Med Chem. 2010 Mar 15;18(6):2152-8. Epub 2010 Feb 6.Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter.
Ref 530988Bioorg Med Chem. 2010 Jun 15;18(12):4422-32. Epub 2010 Apr 29.ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.
Ref 531953LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69.
Ref 533444J Biol Chem. 1988 Jan 5;263(1):187-92.High affinity phlorizin binding to the LLC-PK1 cells exhibits a sodium:phlorizin stoichiometry of 2:1.
Ref 543973(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: 915).
Ref 550963Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).

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