Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTOKC04)

• DTP Name: Sodium/glucose cotransporter 1 (SLC5A1)
• Gene Name: SLC5A1
• UniProt ID: P13866 (SC5A1_HUMAN)
• VARIDT ID: DTD0418
• Synonyms: D22S675; High affinity sodium-glucose cotransporter; NAGT; Na(+)/glucose cotransporter 1; SGLT1; SLC5A1; Solute carrier family 5 member 1
• DTP Family: Solute:Sodium Symporter (SSS) Family
• Tissue Specificity: Expressed mainly in intestine and kidney.
• Sequence:
  MDSSTWSPKTTAVTRPVETHELIRNAADISIIVIYFVVVMAVGLWAMFSTNRGTVGGFFL
  AGRSMVWWPIGASLFASNIGSGHFVGLAGTGAASGIAIGGFEWNALVLVVVLGWLFVPIY
  IKAGVVTMPEYLRKRFGGQRIQVYLSLLSLLLYIFTKISADIFSGAIFINLALGLNLYLA
  IFLLLAITALYTITGGLAAVIYTDTLQTVIMLVGSLILTGFAFHEVGGYDAFMEKYMKAI
  PTIVSDGNTTFQEKCYTPRADSFHIFRDPLTGDLPWPGFIFGMSILTLWYWCTDQVIVQR
  CLSAKNMSHVKGGCILCGYLKLMPMFIMVMPGMISRILYTEKIACVVPSECEKYCGTKVG
  CTNIAYPTLVVELMPNGLRGLMLSVMLASLMSSLTSIFNSASTLFTMDIYAKVRKRASEK
  ELMIAGRLFILVLIGISIAWVPIVQSAQSGQLFDYIQSITSYLGPPIAAVFLLAIFWKRV
  NEPGAFWGLILGLLIGISRMITEFAYGTGSCMEPSNCPTIICGVHYLYFAIILFAISFIT
  IVVISLLTKPIPDVHLYRLCWSLRNSKEERIDLDAEEENIQEGPKETIEIETQVPEKKKG
  IFRRAYDLFCGLEQHGAPKMTEEEEKAMKMKMTDTSEKPLWRTVLNVNGIILVTVAVFCH
  AYFA
• Function: This transporter actively transports glucose into cells by Na(+) cotransport with a Na(+) to glucose coupling ratio of 2:1.
• Endogenous Substrate(s): Galactose; Na+; Water
• TCDB ID: 2.A.21.3.1
• Gene ID: 6523
• KEGG Pathway:
  Carbohydrate digestion and absorption (hsa04973)
  Bile secretion (hsa04976)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM) (R-HSA-5656364)
  Intestinal hexose absorption (R-HSA-8981373)
  Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DTP

1 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-deoxyglucose	DMIAHVU	Solid tumour/cancer	2A00-2F9Z	Approved	[14]

1 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[14]

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	4.72E-01	-2.69E-02	-1.40E-01
Adrenocortical carcinoma	2D11.Z	Kidney	4.32E-01	-3.63E-02	-1.44E-01
Alopecia	ED70	Skin from scalp	2.63E-02	-1.08E-01	-2.92E-01
Alzheimer's disease	8A20	Entorhinal cortex	2.14E-01	-2.06E-02	-1.39E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	6.23E-01	5.30E-02	3.96E-01
Aortic stenosis	BB70	Calcified aortic valve	5.99E-01	-9.76E-02	-1.85E-01
Apnea	7A40	Hyperplastic tonsil	1.30E-02	-1.41E+00	-1.36E+00
Arthropathy	FA00-FA5Z	Peripheral blood	6.06E-03	1.22E-01	1.24E+00
Asthma	CA23	Nasal and bronchial airway	1.61E-01	-1.75E-01	-2.67E-01
Atopic dermatitis	EA80	Skin	5.20E-02	-3.85E-01	-3.25E+00
Autism	6A02	Whole blood	9.55E-01	3.39E-03	1.83E-02
Autoimmune uveitis	9A96	Peripheral monocyte	2.98E-01	-3.16E-02	-2.35E-01
Autosomal dominant monocytopenia	4B04	Whole blood	6.56E-01	-2.11E-02	-1.90E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.86E-07	3.75E-01	7.69E-01
Batten disease	5C56.1	Whole blood	6.12E-03	1.45E-01	2.05E+00
Behcet's disease	4A62	Peripheral blood	8.56E-01	-1.40E-03	-8.23E-03
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.20E-01	-5.82E-02	-3.80E-01
Bladder cancer	2C94	Bladder tissue	7.84E-04	3.60E-01	2.20E+00
Breast cancer	2C60-2C6Z	Breast tissue	5.15E-28	-8.05E-01	-1.18E+00
Cardioembolic stroke	8B11.20	Whole blood	6.81E-04	1.52E-01	1.02E+00
Cervical cancer	2C77	Cervical tissue	9.37E-07	-1.15E+00	-1.95E+00
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.26E-01	7.70E-02	3.81E-01
Chronic hepatitis C	1E51.1	Whole blood	2.31E-01	9.09E-02	4.61E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	5.63E-01	-4.02E-02	-2.14E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	5.41E-01	-4.35E-02	-8.53E-02
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	2.53E-01	3.52E-01	1.14E+00
Colon cancer	2B90	Colon tissue	7.49E-33	9.79E-01	1.55E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.52E-01	2.59E-02	2.02E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	4.65E-01	-1.51E-01	-6.97E-01
Endometriosis	GA10	Endometrium tissue	5.30E-03	1.50E-01	4.17E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	6.60E-01	-3.52E-02	-2.14E-01
Familial hypercholesterolemia	5C80.00	Whole blood	1.56E-03	-1.86E-01	-9.14E-01
Gastric cancer	2B72	Gastric tissue	1.71E-03	1.52E+00	8.02E+00
Glioblastopma	2A00.00	Nervous tissue	5.57E-04	-3.95E-02	-1.58E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.13E-03	-4.85E-01	-2.03E+00
Head and neck cancer	2D42	Head and neck tissue	2.01E-07	-5.94E-01	-1.04E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	2.55E-02	-6.93E-02	-4.00E-01
Huntington's disease	8A01.10	Whole blood	1.38E-01	2.19E-02	3.01E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.23E-01	-1.76E-01	-1.38E+00
Immunodeficiency	4A00-4A20	Peripheral blood	1.27E-01	1.66E-02	3.55E-01
Influenza	1.00E+30	Whole blood	4.25E-01	3.48E-01	1.49E+00
Interstitial cystitis	GC00.3	Bladder tissue	7.00E-01	4.20E-02	2.33E-01
Intracranial aneurysm	8B01.0	Intracranial artery	6.66E-01	-1.06E-02	-7.09E-02
Irritable bowel syndrome	DD91.0	Rectal colon tissue	2.23E-01	-8.66E-04	-3.13E-03
Ischemic stroke	8B11	Peripheral blood	9.90E-01	1.46E-02	1.11E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	2.46E-02	9.75E-02	3.91E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	1.84E-01	5.83E-02	7.45E-01
Lateral sclerosis	8B60.4	Skin	1.63E-03	8.23E-02	2.87E+00
Liver cancer	2C12.0	Liver tissue	5.16E-09	-3.77E-01	-1.66E+00
Liver failure	DB99.7-DB99.8	Liver tissue	9.41E-02	3.71E-01	1.59E+00
Lung cancer	2C25	Lung tissue	1.03E-04	-3.55E-01	-9.28E-01
Lupus erythematosus	4A40	Whole blood	4.55E-02	-1.39E-01	-3.39E-01
Major depressive disorder	6A70-6A7Z	Whole blood	8.56E-02	1.77E-02	8.94E-02
Major depressive disorder	6A70-6A7Z	Hippocampus	6.38E-01	3.63E-02	2.33E-01
Melanoma	2C30	Skin	8.96E-02	-8.92E-01	-8.06E-01
Multiple myeloma	2A83.1	Bone marrow	4.80E-02	-1.86E-01	-1.18E+00
Multiple myeloma	2A83.1	Peripheral blood	8.84E-01	-6.27E-02	-3.53E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	9.41E-02	1.96E-01	7.64E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.02E-01	-4.76E-02	-3.04E-01
Myelofibrosis	2A20.2	Whole blood	8.10E-01	-1.10E-02	-9.23E-02
Myocardial infarction	BA41-BA50	Peripheral blood	3.86E-02	3.71E-01	8.01E-01
Myopathy	8C70.6	Muscle tissue	6.21E-02	1.10E-01	8.51E-01
Neonatal sepsis	KA60	Whole blood	2.78E-02	4.84E-02	2.53E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	9.22E-04	-4.85E-01	-1.42E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	6.79E-01	1.27E-02	8.37E-02
Obesity related type 2 diabetes	5A11	Omental adipose tissue	9.22E-01	2.54E-03	2.51E-02
Olive pollen allergy	CA08.00	Peripheral blood	1.59E-01	2.37E-01	1.10E+00
Oral cancer	2B6E	Oral tissue	8.85E-04	-5.28E-01	-6.28E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	2.78E-01	8.03E-02	3.07E-01
Osteoporosis	FB83.1	Bone marrow	1.80E-01	9.10E-02	1.41E+00
Ovarian cancer	2C73	Ovarian tissue	5.48E-03	3.34E-01	7.08E-01
Pancreatic cancer	2C10	Pancreas	5.79E-01	-1.37E-01	-1.35E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	1.43E-01	-1.11E-01	-9.14E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	4.37E-01	-1.41E-02	-1.21E-01
Pituitary cancer	2D12	Pituitary tissue	9.90E-01	4.23E-02	9.09E-02
Pituitary gonadotrope tumour	2D12	Pituitary tissue	9.54E-01	3.54E-02	6.43E-02
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	4.65E-01	-8.23E-02	-6.59E-01
Polycythemia vera	2A20.4	Whole blood	9.45E-01	3.23E-02	2.39E-01
Pompe disease	5C51.3	Biceps muscle	8.41E-01	1.49E-02	3.09E-02
Preterm birth	KA21.4Z	Myometrium	2.42E-01	1.14E-01	1.30E+00
Prostate cancer	2C82	Prostate	5.57E-01	4.96E-01	4.47E-01
Psoriasis	EA90	Skin	1.30E-47	1.95E+00	4.00E+00
Rectal cancer	2B92	Rectal colon tissue	7.06E-02	5.80E-01	1.30E+00
Renal cancer	2C90-2C91	Kidney	1.98E-01	-3.05E-01	-5.65E-01
Retinoblastoma	2D02.2	Uvea	8.64E-02	-8.70E-02	-5.58E-01
Rheumatoid arthritis	FA20	Synovial tissue	8.46E-01	6.62E-03	1.45E-02
Rhinovirus infection	CA42.1	Nasal epithelium tissue	1.23E-01	-3.62E-02	-1.40E-01
Schizophrenia	6A20	Prefrontal cortex	5.41E-01	-3.71E-02	-1.67E-01
Schizophrenia	6A20	Superior temporal cortex	8.89E-01	-9.43E-04	-1.00E-02
Scleroderma	4A42.Z	Whole blood	7.96E-03	8.93E-02	7.31E-01
Seizure	8A60-8A6Z	Whole blood	4.87E-01	-5.17E-02	-2.66E-01
Sensitive skin	EK0Z	Skin	7.97E-01	4.60E-03	1.00E-02
Sepsis with septic shock	1G41	Whole blood	1.16E-14	1.58E-01	7.80E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.47E-02	4.98E-01	1.33E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	3.73E-02	7.44E-02	3.72E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.38E-01	1.94E-02	3.01E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	9.82E-01	-1.31E-01	-1.83E-01
Skin cancer	2C30-2C3Z	Skin	3.02E-42	-1.19E+00	-2.09E+00
Thrombocythemia	3B63	Whole blood	9.97E-01	6.68E-02	4.96E-01
Thrombocytopenia	3B64	Whole blood	6.24E-01	9.10E-02	6.40E-01
Thyroid cancer	2D10	Thyroid	1.17E-05	9.13E-02	3.95E-01
Tibial muscular dystrophy	8C75	Muscle tissue	1.62E-01	-1.53E-01	-7.66E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	8.42E-01	1.38E-02	1.56E-01
Type 2 diabetes	5A11	Liver tissue	9.67E-01	8.24E-02	4.25E-01
Ureter cancer	2C92	Urothelium	3.86E-01	-2.32E-02	-1.98E-01
Uterine cancer	2C78	Endometrium tissue	2.86E-02	9.53E-03	1.04E-02
Vitiligo	ED63.0	Skin	2.20E-01	-2.08E-01	-5.46E-01

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Sodium/glucose cotransporter 1 (SGLT1) DTT Info
• DTP DTT Type: Clinical trial

1 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sotagliflozin	DMMLXA9	Heart failure	BD10-BD13	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[2]
YG1699	DM1NR1J	Type-1 diabetes	5A10	Phase 2	[3]
1614235 + 2330672	DMD751X	Type-2 diabetes	5A11	Phase 1	[2]
GSK1614235	DM7I1AQ	Type-2 diabetes	5A11	Phase 1	[4]
LX2761	DM8ZS7T	Type 2 diabetes	5A11	Phase 1	[5]

1 Discontinued Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
T-1095	DMGFS51	Diabetic complication	5A2Y	Discontinued in Phase 2	[6]

18 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
10-methoxy-N(1)-methylburnamine-17-O-veratrate	DMJW25X	Discovery agent	N.A.	Investigative	[7]
Acerogenin A	DM4BWMO	Discovery agent	N.A.	Investigative	[8]
ACEROGENIN B	DMVQ30P	Discovery agent	N.A.	Investigative	[8]
Alstiphyllanine D	DM2FLDJ	Discovery agent	N.A.	Investigative	[7]
Alstiphyllanine E	DMTNQ5E	Discovery agent	N.A.	Investigative	[7]
Alstiphyllanine F	DMKRAEW	Discovery agent	N.A.	Investigative	[7]
Burnamine-17-O-3',4',5'-trimethoxybenzoate	DMBO0WI	Discovery agent	N.A.	Investigative	[7]
KURAIDIN	DMLDUJ1	Discovery agent	N.A.	Investigative	[9]
KURARINONE	DMH0G8W	Discovery agent	N.A.	Investigative	[9]
Kushenol N	DMY13UR	Discovery agent	N.A.	Investigative	[9]
O-spiroketal glucoside	DM3FS62	Discovery agent	N.A.	Investigative	[10]
Phlorizin	DMNARGO	Discovery agent	N.A.	Investigative	[11]
QCP	DM62PI8	Discovery agent	N.A.	Investigative	[12]
QCPac	DMSMQXZ	Discovery agent	N.A.	Investigative	[12]
QNEQCPQVSac	DMTY5HP	Discovery agent	N.A.	Investigative	[12]
QSPac	DMJHTUG	Discovery agent	N.A.	Investigative	[12]
sergliflozin	DMF8GAX	Discovery agent	N.A.	Investigative	[13]
Sophoraflavanone G	DMBTMN5	Discovery agent	N.A.	Investigative	[9]

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] ClinicalTrials.gov (NCT04956263) A Comparison of Postprandial Glucose After a Mixed Meal Tolerance Test, and the Metabolic Effects of Insulin Withdrawal in a Crossover Study of the Dual Systemic SGLT1 and SGLT2 Inhibitor YG1699, and the Selective SGLT2 Inhibitor Dapagliflozin in Subjects With Type 1 Diabetes. U.S.National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Clinical pipeline report, company report or official report of Lexicon Pharmaceuticals.
• [6] T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
• [7] 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.
• [8] Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1070-4.
• [9] Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS One. 2014 Feb 26;9(2):e89977.