Target Information
Target General Information | Top | |||||
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Target ID |
T30085
(Former ID: TTDNC00579)
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Target Name |
Sodium/glucose cotransporter 2 (SGLT2)
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Synonyms |
Solute carrier family 5 member 2; Na(+)/glucose cotransporter 2; Low affinity sodium-glucose cotransporter
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Gene Name |
SLC5A2
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Diabetes mellitus [ICD-11: 5A10] | |||||
2 | Heart failure [ICD-11: BD10-BD1Z] | |||||
3 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
Function |
Has a Na(+) to glucose coupling ratio of 1:1. Sodium-dependent glucose transporter.
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BioChemical Class |
Solute:sodium symporter
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UniProt ID | ||||||
Sequence |
MEEHTEAGSAPEMGAQKALIDNPADILVIAAYFLLVIGVGLWSMCRTNRGTVGGYFLAGR
SMVWWPVGASLFASNIGSGHFVGLAGTGAASGLAVAGFEWNALFVVLLLGWLFAPVYLTA GVITMPQYLRKRFGGRRIRLYLSVLSLFLYIFTKISVDMFSGAVFIQQALGWNIYASVIA LLGITMIYTVTGGLAALMYTDTVQTFVILGGACILMGYAFHEVGGYSGLFDKYLGAATSL TVSEDPAVGNISSFCYRPRPDSYHLLRHPVTGDLPWPALLLGLTIVSGWYWCSDQVIVQR CLAGKSLTHIKAGCILCGYLKLTPMFLMVMPGMISRILYPDEVACVVPEVCRRVCGTEVG CSNIAYPRLVVKLMPNGLRGLMLAVMLAALMSSLASIFNSSSTLFTMDIYTRLRPRAGDR ELLLVGRLWVVFIVVVSVAWLPVVQAAQGGQLFDYIQAVSSYLAPPVSAVFVLALFVPRV NEQGAFWGLIGGLLMGLARLIPEFSFGSGSCVQPSACPAFLCGVHYLYFAIVLFFCSGLL TLTVSLCTAPIPRKHLHRLVFSLRHSKEEREDLDADEQQGSSLPVQNGCPESAMEMNEPQ APAPSLFRQCLLWFCGMSRGGVGSPPPLTQEEAAAAARRLEDISEDPSWARVVNLNALLM MAVAVFLWGFYA Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T48DQY |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 6 Approved Drugs | + | ||||
1 | Canagliflozin | Drug Info | Approved | Type-2 diabetes | [2], [3], [4], [5] | |
2 | Dapagliflozin | Drug Info | Approved | Type-2 diabetes | [6], [1], [5] | |
3 | Dapagliflozin Propanediol; Saxagliptin Hydrochloride | Drug Info | Approved | Type-2 diabetes | [7], [5] | |
4 | Empagliflozin | Drug Info | Approved | Type-1 diabetes | [8], [1] | |
5 | PF-04971729 | Drug Info | Approved | Type-2 diabetes | [9] | |
6 | Sotagliflozin | Drug Info | Approved | Heart failure | [10] | |
Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
1 | ASP1941 | Drug Info | Phase 3 | Liver disease | [11] | |
2 | AVE-2268 | Drug Info | Phase 2 | Diabetic complication | [12] | |
3 | LIK-066 | Drug Info | Phase 2 | Type-2 diabetes | [13], [14], [5] | |
4 | Remogliflozin etabonate | Drug Info | Phase 2 | Type-1/2 diabetes | [15] | |
5 | RO-4998452 | Drug Info | Phase 2 | Type-2 diabetes | [16] | |
6 | YG1699 | Drug Info | Phase 2 | Type-1 diabetes | [17] | |
7 | YM-543 | Drug Info | Phase 2 | Type-2 diabetes | [18] | |
8 | BI-44847 | Drug Info | Phase 1 | Type-2 diabetes | [19] | |
9 | EGT-0001474 | Drug Info | Phase 1 | Type-2 diabetes | [20] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | TS-033 | Drug Info | Discontinued in Phase 2 | Diabetic complication | [21] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 14 Modulator drugs | + | ||||
1 | Canagliflozin | Drug Info | [3], [4], [22] | |||
2 | Dapagliflozin | Drug Info | [1], [22] | |||
3 | Dapagliflozin Propanediol; Saxagliptin Hydrochloride | Drug Info | [23] | |||
4 | Empagliflozin | Drug Info | [1] | |||
5 | PF-04971729 | Drug Info | [24] | |||
6 | Sotagliflozin | Drug Info | [10] | |||
7 | ASP1941 | Drug Info | [25], [26] | |||
8 | AVE-2268 | Drug Info | [27] | |||
9 | RO-4998452 | Drug Info | [28] | |||
10 | YM-543 | Drug Info | [29] | |||
11 | BI-44847 | Drug Info | [30] | |||
12 | EGT-0001474 | Drug Info | [31] | |||
13 | TS-033 | Drug Info | [32] | |||
14 | Empagli ozin | Drug Info | [1] | |||
Inhibitor | [+] 4 Inhibitor drugs | + | ||||
1 | LIK-066 | Drug Info | [14], [5] | |||
2 | Remogliflozin etabonate | Drug Info | [5] | |||
3 | YG1699 | Drug Info | [17] | |||
4 | sergliflozin | Drug Info | [33] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Empagliflozin | Ligand Info | |||||
Structure Description | Structure of human SGLT2-MAP17 complex bound with empagliflozin | PDB:7VSI | ||||
Method | Electron microscopy | Resolution | 2.95 Å | Mutation | No | [34] |
PDB Sequence |
DNPADILVIA
30 AYFLLVIGVG40 LWSMCRTNRG50 TVGGYFLAGR60 SMVWWPVGAS70 LFASNIGSGH 80 FVGLAGTGAA90 SGLAVAGFEW100 NALFVVLLLG110 WLFAPVYLTA120 GVITMPQYLR 130 KRFGGRRIRL140 YLSVLSLFLY150 IFTKISVDMF160 SGAVFIQQAL170 GWNIYASVIA 180 LLGITMIYTV190 TGGLAALMYT200 DTVQTFVILG210 GACILMGYAF220 HEVGGYSGLF 230 DKYLGAATSL240 TVSEDPAVGN250 ISSFCYRPRP260 DSYHLLRHPV270 TGDLPWPALL 280 LGLTIVSGWY290 WCSDQVIVQR300 CLAGKSLTHI310 KAGCILCGYL320 KLTPMFLMVM 330 PGMISRILYP340 DEVACVVPEV350 CRRVCGTEVG360 CSNIAYPRLV370 VKLMPNGLRG 380 LMLAVMLAAL390 MSSLASIFNS400 SSTLFTMDIY410 TRLRPRAGDR420 ELLLVGRLWV 430 VFIVVVSVAW440 LPVVQAAQGG450 QLFDYIQAVS460 SYLAPPVSAV470 FVLALFVPRV 480 NEQGAFWGLI490 GGLLMGLARL500 IPEFSFGSGS510 CVQPSACPAF520 LCGVHYLYFA 530 IVLFFCSGLL540 TLTVSLCTAP550 IPRKHLHRLV560 FSLRHSKEER570 EDLDEDISED 646 PSWARVVNLN656 ALLMMAVAVF666 LWGFYA
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ASN75
3.274
GLY79
4.021
HIS80
3.181
GLY83
3.564
LEU84
3.413
THR87
3.408
VAL95
3.319
PHE98
2.403
GLU99
3.242
ALA102
3.736
THR153
4.471
VAL157
3.728
LEU274
3.838
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Affiliated Biological Pathways | Top | |||||
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Reactome | [+] 3 Reactome Pathways | + | ||||
1 | Hexose transport | |||||
2 | Na+-dependent glucose transporters | |||||
3 | Inositol transporters | |||||
WikiPathways | [+] 3 WikiPathways | + | ||||
1 | NRF2 pathway | |||||
2 | Nuclear Receptors Meta-Pathway | |||||
3 | Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds |
References | Top | |||||
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REF 1 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
REF 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. (Ligand id: 4582). | |||||
REF 3 | Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651. | |||||
REF 4 | Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial. Metabolism. 2014 Oct;63(10):1296-303. | |||||
REF 5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 6 | 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. (Ligand id: 4594). | |||||
REF 7 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018 | |||||
REF 8 | 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. (Ligand id: 4754). | |||||
REF 9 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
REF 10 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216203. | |||||
REF 11 | ClinicalTrials.gov (NCT01054092) A Study to Assess the Long-term Safety and Efficacy of ASP1941 in Japanese Diabetic Patients. U.S. National Institutes of Health. | |||||
REF 12 | ClinicalTrials.gov (NCT00361738) Dose-Ranging Study Evaluating AVE2268 in Patients With Type 2 Diabetes Not Adequately Controlled by a Metformin Treatment. U.S. National Institutes of Health. | |||||
REF 13 | ClinicalTrials.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 14 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021813) | |||||
REF 16 | ClinicalTrials.gov (NCT00800176) A Dose-Finding Study of RO4998452 in Patients With Diabetes Mellitus. U.S. National Institutes of Health. | |||||
REF 17 | 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. | |||||
REF 18 | ClinicalTrials.gov (NCT00454233) A Safety and Efficacy Study With YM543 in Type 2 Diabetes Mellitus Subjects. U.S. National Institutes of Health. | |||||
REF 19 | ClinicalTrials.gov (NCT02211937) Relative Oral Bioavailability of BI 44847 as Suspension Compared to Tablet and the Influence of Food Anf of BI 44847 as Solution Compared to Tablet in Healthy Male Volunteers. U.S. National Institutes of Health. | |||||
REF 20 | ClinicalTrials.gov (NCT00854113) Study to Determine the Safety, Tolerability, and Pharmacokinetic (PK) Profile of EGT0001474 in Healthy Volunteers. U.S. National Institutes of Health. | |||||
REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021799) | |||||
REF 22 | Canagliflozin-current status in the treatment of type 2 diabetes mellitus with focus on clinical trial data.World J Diabetes.2014 Jun 15;5(3):399-406. | |||||
REF 23 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
REF 24 | Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin.Diabetes Obes Metab.2015 Jun;17(6):591-8. | |||||
REF 25 | Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan.World J Diabetes.2015 Feb 15;6(1):136-44. | |||||
REF 26 | Efficacy and safety of ipragliflozin in patients with type 2 diabetes inadequately controlled on metformin: a dose-finding study.Diabetes Obes Metab. 2013 May;15(5):403-9. | |||||
REF 27 | Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats. Arzneimittelforschung. 2008;58(11):574-80. | |||||
REF 28 | A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.Diabetes Obes Metab.2015 Oct;17(10):984-93. | |||||
REF 29 | Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor. Endocr Res. 2013 Aug;38(3):168-183. | |||||
REF 30 | Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes | |||||
REF 31 | PhRMA report | |||||
REF 32 | Company report (Taisho) | |||||
REF 33 | 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. | |||||
REF 34 | Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature. 2022 Jan;601(7892):280-284. |
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