Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2UE56)

• DTT Name: Sodium/glucose cotransporter 1 (SGLT1)
• Synonyms: Solute carrier family 5 member 1; Na(+)/glucose cotransporter 1; NAGT; High affinity sodium-glucose cotransporter
• Gene Name: SLC5A1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Cardiovascular disease [ICD-11: BA00-BE2Z]
  Diabetes mellitus [ICD-11: 5A10]
  Type 2 diabetes mellitus [ICD-11: 5A11]
• BioChemical Class: Solute:sodium symporter
• UniProt ID: SC5A1_HUMAN
• TTD ID: T54771
• Sequence:
  MDSSTWSPKTTAVTRPVETHELIRNAADISIIVIYFVVVMAVGLWAMFSTNRGTVGGFFL
  AGRSMVWWPIGASLFASNIGSGHFVGLAGTGAASGIAIGGFEWNALVLVVVLGWLFVPIY
  IKAGVVTMPEYLRKRFGGQRIQVYLSLLSLLLYIFTKISADIFSGAIFINLALGLNLYLA
  IFLLLAITALYTITGGLAAVIYTDTLQTVIMLVGSLILTGFAFHEVGGYDAFMEKYMKAI
  PTIVSDGNTTFQEKCYTPRADSFHIFRDPLTGDLPWPGFIFGMSILTLWYWCTDQVIVQR
  CLSAKNMSHVKGGCILCGYLKLMPMFIMVMPGMISRILYTEKIACVVPSECEKYCGTKVG
  CTNIAYPTLVVELMPNGLRGLMLSVMLASLMSSLTSIFNSASTLFTMDIYAKVRKRASEK
  ELMIAGRLFILVLIGISIAWVPIVQSAQSGQLFDYIQSITSYLGPPIAAVFLLAIFWKRV
  NEPGAFWGLILGLLIGISRMITEFAYGTGSCMEPSNCPTIICGVHYLYFAIILFAISFIT
  IVVISLLTKPIPDVHLYRLCWSLRNSKEERIDLDAEEENIQEGPKETIEIETQVPEKKKG
  IFRRAYDLFCGLEQHGAPKMTEEEEKAMKMKMTDTSEKPLWRTVLNVNGIILVTVAVFCH
  AYFA
• Function: 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. Actively transports glucose into cells by Na(+) cotransport with a Na(+) to glucose coupling ratio of 2:1.
• KEGG Pathway:
  Carbohydrate digestion and absorption (hsa04973)
  Bile secretion (hsa04976)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Na+-dependent glucose transporters (R-HSA-428808)
  Inositol transporters (R-HSA-429593)
  Hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LX-4211	DMMLXA9	Cardiovascular disease	BA00-BE2Z	Phase 3	[1]
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[2]
1614235 + 2330672	DMD751X	Type-2 diabetes	5A11	Phase 1	[2]
GSK1614235	DM7I1AQ	Type-2 diabetes	5A11	Phase 1	[3]
LX2761	DM8ZS7T	Type 2 diabetes	5A11	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
T-1095	DMGFS51	Diabetic complication	5A2Y	Discontinued in Phase 2	[5]

18 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
10-methoxy-N(1)-methylburnamine-17-O-veratrate	DMJW25X	Discovery agent	N.A.	Investigative	[6]
Acerogenin A	DM4BWMO	Discovery agent	N.A.	Investigative	[7]
Acerogenin B	DMVQ30P	Discovery agent	N.A.	Investigative	[7]
Alstiphyllanine D	DM2FLDJ	Discovery agent	N.A.	Investigative	[6]
Alstiphyllanine E	DMTNQ5E	Discovery agent	N.A.	Investigative	[6]
Alstiphyllanine F	DMKRAEW	Discovery agent	N.A.	Investigative	[6]
Burnamine-17-O-3',4',5'-trimethoxybenzoate	DMBO0WI	Discovery agent	N.A.	Investigative	[6]
Kuraidin	DMLDUJ1	Discovery agent	N.A.	Investigative	[8]
Kurarinone	DMH0G8W	Discovery agent	N.A.	Investigative	[8]
Kushenol N	DMY13UR	Discovery agent	N.A.	Investigative	[8]
O-spiroketal glucoside	DM3FS62	Discovery agent	N.A.	Investigative	[9]
Phlorizin	DMNARGO	Discovery agent	N.A.	Investigative	[10]
QCP	DM62PI8	Discovery agent	N.A.	Investigative	[11]
Qcpac	DMSMQXZ	Discovery agent	N.A.	Investigative	[11]
QNEQCPQVSac	DMTY5HP	Discovery agent	N.A.	Investigative	[11]
QSPac	DMJHTUG	Discovery agent	N.A.	Investigative	[11]
sergliflozin	DMF8GAX	Discovery agent	N.A.	Investigative	[12]
Sophoraflavanone G	DMBTMN5	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	9.67E-01	0.08	0.42

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Sodium/glucose cotransporter 1 (SLC5A1) DTP Info
• Gene Name: SLC5A1

1 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-deoxyglucose	DMIAHVU	Solid tumour/cancer	2A00-2F9Z	Approved	[13]

1 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[13]

References

• [1] LX4211, 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.
• [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. (Target id: 915).
• [3] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [4] Clinical pipeline report, company report or official report of Lexicon Pharmaceuticals.
• [5] T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
• [6] Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter. Bioorg Med Chem. 2010 Mar 15;18(6):2152-2158.
• [7] Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1070-4.
• [8] Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
• [9] ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors. Bioorg Med Chem. 2010 Jun 15;18(12):4422-32.
• [10] J 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.
• [11] Tripeptides of RS1 (RSC1A1) inhibit a monosaccharide-dependent exocytotic pathway of Na+-D-glucose cotransporter SGLT1 with high affinity. J Biol Chem. 2007 Sep 28;282(39):28501-13.
• [12] Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal gluco... J Pharmacol Exp Ther. 2007 Jan;320(1):323-30.
• [13] The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS One. 2014 Feb 26;9(2):e89977.