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Sodium/glucose cotransporter 2

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Target not currently curated in GtoImmuPdb

Target id: 916

Nomenclature: Sodium/glucose cotransporter 2

Abbreviated Name: SGLT2

Systematic Nomenclature: SLC5A2

Family: Hexose transporter family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 11 672 16p11.2 SLC5A2 solute carrier family 5 member 2
Mouse 11 670 7 F3 Slc5a2 solute carrier family 5 (sodium/glucose cotransporter), member 2
Rat 11 670 1q37 Slc5a2 solute carrier family 5 member 2
Previous and Unofficial Names Click here for help
low affinity sodium-glucose cotransporter | low affinity Na-dependent glucose transporter (SGLT2) | Na(+)/glucose cotransporter 2 | solute carrier family 5 member 2 | solute carrier family 5 (sodium/glucose cotransporter), member 2 | solute carrier family 5 (sodium/glucose cotransporter)
Database Links Click here for help
Specialist databases
Bioparadigms SLC Tables SLC5A2 (Hs)
RESOLUTE SLC5A2 (Hs)
Other databases
Alphafold P31639 (Hs), Q923I7 (Mm), P53792 (Rn)
ChEMBL Target CHEMBL3884 (Hs), CHEMBL1075302 (Mm), CHEMBL4316 (Rn)
DrugBank Target P31639 (Hs)
Ensembl Gene ENSG00000140675 (Hs), ENSMUSG00000030781 (Mm), ENSRNOG00000020039 (Rn)
Entrez Gene 6524 (Hs), 246787 (Mm), 64522 (Rn)
Human Protein Atlas ENSG00000140675 (Hs)
KEGG Gene hsa:6524 (Hs), mmu:246787 (Mm), rno:64522 (Rn)
OMIM 182381 (Hs)
Pharos P31639 (Hs)
UniProtKB P31639 (Hs), Q923I7 (Mm), P53792 (Rn)
Wikipedia SLC5A2 (Hs)
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
D-glucose Hs -
α-MDG Hs -
Stoichiometry Click here for help
1 Na+ : 1 glucose [6]

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
remogliflozin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.9 pKi 4
⤷ pKi 7.9 (Ki 1.24x10-8 M) [4]
sergliflozin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.8 pKi 8
⤷ pKi 6.8 (Ki 1.58x10-7 M) [8]
dapagliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pIC50 7
⤷ pIC50 9.3 (IC50 4.9x10-10 M) [7]
licogliflozin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.3 pIC50 1
⤷ pIC50 9.3 (IC50 5x10-10 M) [1]
Description: Measuring inhibition of sodium-dependent [14]C- alpha-methyl-glucopyranoside (AMG) transport into the interior of cells transfected with hSGLT2.
enavogliflozin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 3
⤷ pIC50 9.1 (IC50 8x10-10 M) [3]
Description: Determined by measuring the uptake of the substrate methyl a-D-glucopyranoside (AMG) in CHO cells expressing hSGLT2.
ertugliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 10
⤷ pIC50 9.1 (IC50 8.77x10-10 M) [10]
sotagliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 14
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [14]
bexagliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.6 pIC50 13
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [13]
tofogliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.5 pIC50 11
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [11]
Description: Measuring inhibition of sodium-dependent [14C]AMG-uptake in CHO cells expressing hSGLT2.
empagliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 5
⤷ pIC50 8.5 (IC50 3.2x10-9 M) [5]
canagliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 4.4x10-9 M) [9]
ipragliflozin Small molecule or natural product Approved drug Click here for species-specific activity table Mm Inhibition 8.3 pIC50 12
⤷ pIC50 8.3 (IC50 5.64x10-9 M) [12]
Description: Measuring inhibition of sodium-dependent [14C]AMG-uptake in CHO cells expressing mSGLT2.
ipragliflozin Small molecule or natural product Approved drug Click here for species-specific activity table Rn Inhibition 8.2 pIC50 12
⤷ pIC50 8.2 (IC50 6.37x10-9 M) [12]
Description: Measuring inhibition of sodium-dependent [14C]AMG-uptake in CHO cells expressing rSGLT2.
ipragliflozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 12
⤷ pIC50 8.1 (IC50 7.38x10-9 M) [12]
Description: Measuring inhibition of sodium-dependent [14C]AMG-uptake in CHO cells expressing hSGLT2.
View species-specific inhibitor tables
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Renal glucosuria
Synonyms: Renal glycosuria [Disease Ontology: DOID:9432]
Disease Ontology: DOID:9432
OMIM: 233100
Orphanet: ORPHA69076
References:  2

References

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1. Bebernitz GR, Bock MG, Reddy DS, Hajare AK, Vyavahare V, Bhosale B, Kurhade SE, Salunkhe V, Shaikh NS, Bhuniya D et al.. (2011) Glycoside derivatives and uses thereof. Patent number: WO2011048112A1. Assignee: Novartis Ag. Priority date: 20/10/2009. Publication date: 28/04/2011.

2. Calado J, Soto K, Clemente C, Correia P, Rueff J. (2004) Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria. Hum Genet, 114 (3): 314-6. [PMID:14614622]

3. Choi MK, Nam SJ, Ji HY, Park MJ, Choi JS, Song IS. (2020) Comparative Pharmacokinetics and Pharmacodynamics of a Novel Sodium-Glucose Cotransporter 2 Inhibitor, DWP16001, with Dapagliflozin and Ipragliflozin. Pharmaceutics, 12 (3): 268. [PMID:32183468]

4. Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H, Isaji M. (2008) Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther, 327 (1): 268-76. [PMID:18583547]

5. Grempler R, Thomas L, Eckhardt M, Himmelsbach F, Sauer A, Sharp DE, Bakker RA, Mark M, Klein T, Eickelmann P. (2012) Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab, 14 (1): 83-90. [PMID:21985634]

6. Hummel CS, Lu C, Loo DD, Hirayama BA, Voss AA, Wright EM. (2011) Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol, Cell Physiol, 300 (1): C14-21. [PMID:20980548]

7. Kang SY, Song KS, Lee J, Lee SH, Lee J. (2010) Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors. Bioorg Med Chem, 18 (16): 6069-79. [PMID:20637636]

8. Katsuno K, Fujimori Y, Takemura Y, Hiratochi M, Itoh F, Komatsu Y, Fujikura H, Isaji M. (2007) Sergliflozin, 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, 320 (1): 323-30. [PMID:17050778]

9. Liang Y, Arakawa K, Ueta K, Matsushita Y, Kuriyama C, Martin T, Du F, Liu Y, Xu J, Conway B et al.. (2012) Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS ONE, 7 (2): e30555. [PMID:22355316]

10. Mascitti V, Maurer TS, Robinson RP, Bian J, Boustany-Kari CM, Brandt T, Collman BM, Kalgutkar AS, Klenotic MK, Leininger MT et al.. (2011) Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. J Med Chem, 54 (8): 2952-60. [PMID:21449606]

11. Ohtake Y, Sato T, Kobayashi T, Nishimoto M, Taka N, Takano K, Yamamoto K, Ohmori M, Yamaguchi M, Takami K et al.. (2012) Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem, 55 (17): 7828-40. [PMID:22889351]

12. Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Qun L, Tomiyama H et al.. (2012) Pharmacological profile of ipragliflozin (ASP1941), a novel selective SGLT2 inhibitor, in vitro and in vivo. Naunyn Schmiedebergs Arch Pharmacol, 385 (4): 423-36. [PMID:22139434]

13. Xu B, Feng Y, Cheng H, Song Y, Lv B, Wu Y, Wang C, Li S, Xu M, Du J et al.. (2011) C-aryl glucosides substituted at the 4'-position as potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. Bioorg Med Chem Lett, 21 (15): 4465-70. [PMID:21737266]

14. Zambrowicz B, Freiman J, Brown PM, Frazier KS, Turnage A, Bronner J, Ruff D, Shadoan M, Banks P, Mseeh F et al.. (2012) LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther, 92 (2): 158-69. [PMID:22739142]

How to cite this page

Hexose transporter family: Sodium/glucose cotransporter 2. Last modified on 25/01/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=916.