SLC5A2

Summary

SLC5A2 (solute carrier family 5 member 2, HGNC:11037) is a protein-coding gene on chromosome 16p11.2, encoding Sodium/glucose cotransporter 2 (P31639). Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1.

This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene.

Source: NCBI Gene 6524 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial renal glucosuria (Definitive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 310 total — 12 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11037
Approved symbol	SLC5A2
Name	solute carrier family 5 member 2
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140675
Ensembl biotype	protein_coding
OMIM	182381
Entrez	6524

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 retained_intron, 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000330498, ENST00000419665, ENST00000562006, ENST00000564197, ENST00000565446, ENST00000567051, ENST00000568188, ENST00000568891, ENST00000569576, ENST00000865380

RefSeq mRNA: 1 — MANE Select: NM_003041 NM_003041

CCDS: CCDS10714

Canonical transcript exons

ENST00000330498 — 14 exons

Exon	Start	End
ENSE00000944354	31484819	31484923
ENSE00000944356	31486170	31486275
ENSE00000944357	31487320	31487400
ENSE00000944358	31487530	31487759
ENSE00000944360	31488383	31488490
ENSE00000944362	31488880	31489048
ENSE00001602638	31488038	31488173
ENSE00001638541	31488622	31488772
ENSE00001769280	31490309	31490769
ENSE00003489247	31489123	31489338
ENSE00003500491	31485729	31485893
ENSE00003615624	31484673	31484744
ENSE00003621195	31490104	31490230
ENSE00003841615	31483123	31483262

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 91.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0477 / max 35.1447, expressed in 8 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153840	0.0315	3
153841	0.0163	8

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	91.35	gold quality
adult mammalian kidney	UBERON:0000082	90.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.74	gold quality
kidney epithelium	UBERON:0004819	88.71	gold quality
type B pancreatic cell	CL:0000169	86.27	gold quality
olfactory bulb	UBERON:0002264	85.87	gold quality
kidney	UBERON:0002113	85.84	gold quality
renal glomerulus	UBERON:0000074	85.19	gold quality
metanephric glomerulus	UBERON:0004736	85.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.40	gold quality
colonic epithelium	UBERON:0000397	83.82	gold quality
left testis	UBERON:0004533	83.35	gold quality
cervix squamous epithelium	UBERON:0006922	82.71	gold quality
right testis	UBERON:0004534	82.38	gold quality
diaphragm	UBERON:0001103	82.10	gold quality
testis	UBERON:0000473	81.56	gold quality
bone marrow cell	CL:0002092	81.39	gold quality
cortex of kidney	UBERON:0001225	81.31	gold quality
triceps brachii	UBERON:0001509	81.26	gold quality
gluteal muscle	UBERON:0002000	80.44	silver quality
tongue squamous epithelium	UBERON:0006919	79.21	gold quality
vastus lateralis	UBERON:0001379	78.67	gold quality
metanephros	UBERON:0000081	78.60	gold quality
quadriceps femoris	UBERON:0001377	77.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.67	gold quality
oocyte	CL:0000023	76.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.91	gold quality
cervix epithelium	UBERON:0004801	75.46	gold quality
upper arm skin	UBERON:0004263	74.65	gold quality
nasal cavity epithelium	UBERON:0005384	74.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, SMAD3, SP1

miRNA regulators (miRDB)

4 targeting SLC5A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-5002-3P	95.75	67.04	542

Literature-anchored findings (GeneRIF, showing 40)

• Encodes a claudin that localizes to septate junctions and is required for septate junction organization and paracellular barrier function. (Sinuous) (PMID:14734539)
• SGLT2 plays an important role in renal tubular glucose reabsorption. (PMID:14569097)
• homozygous missense mutation in exon 8 of SLC5A2, resulting in a lysine to arginine substitution at position 321 underlies autosomal-recessive renal glucosuria and aminoaciduria (PMID:15610225)
• Thioglycoside I (phenyl-1’-thio-beta-D-glucopyranoside) inhibited hSGLT2. (PMID:17505558)
• Within 17 pedigrees, we have identified a total of 20 different SLC5A2 mutations in familial renal glucosuria. (PMID:18622023)
• The role of SGLT1 and SGLT2 in renal glucose reabsorption are discussed. (PMID:20980548)
• The role of SGLT1 and SGLT2 in renal glucose reabsorption, and the potential for targeting these transporters in diabetes there are discussed. (PMID:21048164)
• Five novel SGLT2 mutations were identified in familial renal glucosuria patients. Mutant SGLT2 proteins had significantly lower glucose transport capacity upon reconstruction in cultured cells. (PMID:21165652)
• TS-071 inhibited SGLT2 activity in a concentration-dependent manner. (PMID:21410690)
• Our data suggest a role of SGLT2 genetic variation in the regulation of glucose homeostasis and promote pharmacogenomic studies to clarify the efficacy of antidiabetic treatment by SGLT2 inhibitors (PMID:21830867)
• analysis of SGLT2 inhibitors containing the 1,2,3-triazole motif and evaluation of their urinary glucose excretion (PMID:22079028)
• A total of 21 different SLC5A2 mutations were detected in a cohort of 23 unrelated Korean children with Familial renal glucosuria (PMID:22314875)
• In this review, we summarize the available data concerning the mechanism of action, efficacy, and safety of this novel antidiabetic class of therapeutic agents. (PMID:22528597)
• It was concluded that human SGLT1 and SGLT2 are regulated by different mechanisms and suggest that insulin is an SGLT2 agonist in vivo. (PMID:22673616)
• Data suggest that SGLT2 plays role in tubular apoptosis in diabetic nephropathy; SGLT2-mediated, high glucose-induced generation of reactive oxygen species appears to augment apoptosis of renal tubular cells. (PMID:23508966)
• Sodium glucose cotransporter 2 inhibitor empagliflozin is not associated with prolonged QT interval. (PMID:23617452)
• A possible role of common genetic variation in SLC5A2 in the control of glucose homeostasis. (PMID:23651029)
• Studies indcate that glucose is present in the glomerular filtrate and is reabsorbed by a group of transport proteins in the renal tubular epithelium, with sodium glucose transporter (SGLT)-2 quantitatively the most important. (PMID:23714218)
• A single dose of canagliflozin, a sodium glucose co-transporter 2 inhibitor, 300 mg reduced both fasting and postprandial PG. (PMID:25110280)
• Results identified six SLC5A2 variants including four novel variants in Chinese familial renal glucosuria. Variant SLC5A2 proteins had altered expression levels and patterns in addition to significantly lower glucose transport in cultured cells. (PMID:25339128)
• SGLT2 inhibitor canagliflozin can be coadministered with oral contraceptives, warfarin, or digoxin without dose adjustments. (PMID:25345427)
• SGLT2 is inhibited with dapagliflozin in pancreatic alpha cells, which triggers glucagon secretion (PMID:25894829)
• SGLT2 is functionally expressed in pancreatic and prostate adenocarcinomas (PMID:26170283)
• Data show that thiosugars bind to sodium-glucose co-transporters vSGLT and hSGLT2 stronger and dissociate more slowly than sugars. (PMID:26260238)
• Data suggest that SGLT2 is transporter found in proximal renal tubules, responsible for reabsorption of most of glucose filtered by kidney; inhibition of SGLT2 lowers blood glucose level by promoting urinary excretion of excess glucose. [REVIEW] (PMID:26362302)
• Data suggest that SGLT2 plays central role in energy metabolism and renal elimination of circulating glucose; targeted inhibition of SGLT2 alters energy metabolism in diabetes and obesity. (PMID:26403227)
• Mutations in the SLC5A2 gene did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. (PMID:26735923)
• Data suggest that, by shunting substantial amounts of carbohydrate into urine, SGLT2-mediated glycosuria results in a progressive shift in energy metabolism toward fatty substrates; studies were conducted in subjects with/without diabetes type 2 treated with SGLT2 antagonist and hypoglycemic agent empagliflozin. (PMID:26861783)
• In both men and women, grip strength increased in both hands after sodium-glucose cotransporter 2 protein (SGLT2) inhibitor treatment . (PMID:27038414)
• Data suggest that ketoacidosis (ketonuria/ketonemia) associated with the use of sodium-glucose cotransporter 2 protein (SGLT-2) inhibitors needs further research. (PMID:27085074)
• C-peptide-based measurements of insulin secretion are appropriate for assessing beta-cell function in SGLT2 inhibitor canagliflozin-treated participants. (PMID:27127999)
• Canagliflozin, an orally active inhibitor of sodium glucose co-transporter 2, is approved for the treatment of type-2 diabetes mellitus. Food did not affect canagliflozin pharmacokinetics. (PMID:27136908)
• Studies indicate that Sodium-glucose cotransporter 2 (SGLT2)T2 inhibitors are promising antidiabetic agents that are gaining attention in both clinical medicine and basic research. (PMID:27754601)
• Results provide evidence that common genetic variants in the SLC5A2 gene do not affect diabetes-related metabolic traits in subjects at increased risk of type 2 diabetes. (PMID:28134748)
• Findings suggest that there are subtypes of T2DM characterized by different urinary glucose excretion and cardiovascular risk factors. SLC5A2 and HNF1A mutations partially explain renal glycosuria in patients with T2DM. (PMID:28324025)
• The novel pathogenic SLC5A2 mutation p.S293C was responsible for the onset of FRG (PMID:28365451)
• Molecular Interaction of Anti-Diabetic Drugs With Acetylcholinesterase and Sodium Glucose Co-Transporter 2. (PMID:28387957)
• In this study, more than 90% of patients were on Forxiga or Invokana. Merck and Pfizer are also collaborating to bring an SGLT2 rival drug, ertugliflozin, to market as well as on two combinations containing the drug to treat type 2 diabetes. (PMID:28398306)
• SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients. (PMID:28399981)
• Data suggest that SGLT2 expression is higher in control kidney than in kidney from subjects with type 2 diabetes; SGLT1 expression in kidney tended in the same direction; SGLT2 appears to be localized to tubular brush-border membranes; unaffected renal tissues were obtained from subjects undergoing unilateral nephrectomy for renal carcinomas. (PMID:28419670)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc5a2	ENSDARG00000100919
mus_musculus	Slc5a2	ENSMUSG00000030781
rattus_norvegicus	Slc5a2	ENSRNOG00000020039
drosophila_melanogaster	CG2187	FBGN0017448
drosophila_melanogaster	rumpel	FBGN0029950
drosophila_melanogaster	SLC5A11	FBGN0031998
drosophila_melanogaster	bumpel	FBGN0037895
drosophila_melanogaster	ChT	FBGN0038641
drosophila_melanogaster	salt	FBGN0039872
drosophila_melanogaster	Smvt	FBGN0039873
drosophila_melanogaster	CG31262	FBGN0051262
drosophila_melanogaster	CG31668	FBGN0051668
drosophila_melanogaster	CG33124	FBGN0053124
drosophila_melanogaster	kumpel	FBGN0250757
caenorhabditis_elegans		WBGENE00000501

Paralogs (12): SLC5A1 (ENSG00000100170), SLC5A4 (ENSG00000100191), SLC5A5 (ENSG00000105641), SLC5A7 (ENSG00000115665), SLC5A9 (ENSG00000117834), SLC5A6 (ENSG00000138074), SLC5A12 (ENSG00000148942), SLC5A10 (ENSG00000154025), SLC5A11 (ENSG00000158865), SLC5A3 (ENSG00000198743), SLC5A8 (ENSG00000256870), (ENSG00000293606)

Protein

Protein identifiers

Sodium/glucose cotransporter 2 — P31639 (reviewed: P31639)

Alternative names: Low affinity sodium-glucose cotransporter, Solute carrier family 5 member 2

All UniProt accessions (2): P31639, H3BP44

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Unlike SLC5A1/SGLT1, requires the auxiliary protein PDZK1IP1/MAP17 for full transporter activity. Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney.

Subunit / interactions. Forms a heterodimer (via TM13) with PDZK1IP1 (via N-terminal transmembrane helix); this interaction enhances SLC5A2 transporter activity.

Subcellular location. Apical cell membrane.

Disease relevance. Renal glucosuria (GLYS) [MIM:233100] A disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Enhanced by the interaction with PDZK1IP1/MAP17. Inhibited by natural product phlorizin and diabetic drugs, including empagliflozin and dapagliflozin, canagliflozin, and sotagliflozin. Empagliflozin is selective for SLC5A2/SGLT2 over SLC5A1/SGLT1 and it inhibits by occupying the sugar-binding site in SLC5A2.

Similarity. Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P31639-1	1	yes
P31639-2	2

RefSeq proteins (1): NP_003032* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001734	Na/solute_symporter	Family
IPR018212	Na/solute_symporter_CS	Conserved_site
IPR038377	Na/Glc_symporter_sf	Homologous_superfamily

Pfam: PF00474

Catalyzed reactions (Rhea), 1 shown:

• D-glucose(out) + Na(+)(out) = D-glucose(in) + Na(+)(in) (RHEA:70571)

UniProt features (97 total): helix 36, topological domain 14, transmembrane region 14, mutagenesis site 7, strand 7, binding site 5, turn 5, disulfide bond 4, splice variant 2, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
9KMN	ELECTRON MICROSCOPY	2.47
9KKQ	ELECTRON MICROSCOPY	2.6
8HEZ	ELECTRON MICROSCOPY	2.8
8HB0	ELECTRON MICROSCOPY	2.9
9KKW	ELECTRON MICROSCOPY	2.92
7VSI	ELECTRON MICROSCOPY	2.95
8HDH	ELECTRON MICROSCOPY	3.1
8HG7	ELECTRON MICROSCOPY	3.1
9KL0	ELECTRON MICROSCOPY	3.16
8HIN	ELECTRON MICROSCOPY	3.3
7YNJ	ELECTRON MICROSCOPY	3.33
7YNK	ELECTRON MICROSCOPY	3.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31639-F1	84.32	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 73; 76; 389; 392; 393

Disulfide bonds (4): 255–511, 345–351, 355–361, 517–522

Glycosylation sites (1): 250

Mutagenesis-validated functional residues (7):

Position	Phenotype
74	impairs phlorizin binding and its inhibition on glucose uptake.
95	strong reduction in d-glucose transporter activity. impairs inhibition by empagliflozin on glucose uptake.
98	slightly decreases d-glucose transporter activity. abolishes empagliflozin binding and its inhibition on glucose uptake.
157	decreases d-glucose transporter activity. impairs inhibition by empagliflozin on glucose uptake.
201	impairs phlorizin binding and its inhibition on glucose uptake.
283	strong reduction in d-glucose transporter activity. impairs inhibition by empagliflozin on glucose uptake.
453	slightly decreases d-glucose transporter activity. impairs empagliflozin binding and its inhibition on glucose uptake. i

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-5658208	Defective SLC5A2 causes renal glucosuria (GLYS1)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 168 (showing top): MORF_RAGE, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_45, MORF_ESR1, MODULE_16, GOBP_MONOATOMIC_CATION_TRANSPORT, MORF_FANCG, chr16p11, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, MODULE_157, TGANTCA_AP1_C, GOCC_APICAL_PLASMA_MEMBRANE, MORF_PML, MORF_IKBKG

GO Biological Process (10): alpha-glucoside transport (GO:0000017), carbohydrate metabolic process (GO:0005975), sodium ion transport (GO:0006814), hexose transmembrane transport (GO:0008645), renal D-glucose absorption (GO:0035623), D-glucose import across plasma membrane (GO:0098708), sodium ion import across plasma membrane (GO:0098719), monoatomic ion transport (GO:0006811), transmembrane transport (GO:0055085), D-glucose transmembrane transport (GO:1904659)

GO Molecular Function (9): low-affinity D-glucose:sodium symporter activity (GO:0005362), D-glucose:sodium symporter activity (GO:0005412), alpha-glucoside transmembrane transporter activity (GO:0015151), metal ion binding (GO:0046872), D-glucose transmembrane transporter activity (GO:0055056), protein binding (GO:0005515), symporter activity (GO:0015293), solute:sodium symporter activity (GO:0015370), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
SLC transporter disorders	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
D-glucose transmembrane transport	2
transport	2
glucoside transport	1
primary metabolic process	1
metal ion transport	1
monosaccharide transmembrane transport	1
renal absorption	1
hexose import across plasma membrane	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
cellular process	1
hexose transmembrane transport	1
D-glucose:sodium symporter activity	1
carbohydrate:monoatomic cation symporter activity	1
solute:sodium symporter activity	1
D-glucose transmembrane transporter activity	1
alpha-glucoside transport	1
glucoside transmembrane transporter activity	1
cation binding	1
hexose transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
solute:monoatomic cation symporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
extracellular vesicle	1

Protein interactions and networks

STRING

1533 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC5A2	DPP4	P27487	909
SLC5A2	GLP1R	P43220	908
SLC5A2	ADCY7	P51828	903
SLC5A2	GCG	P01275	883
SLC5A2	INS	P01308	881
SLC5A2	SLC6A2	P23975	832
SLC5A2	SLC2A2	P11168	812
SLC5A2	SI	P14410	810
SLC5A2	MGAM	O43451	796
SLC5A2	REN	P00797	795
SLC5A2	SLC9A3	P48764	794
SLC5A2	ACE	P12821	773
SLC5A2	SLC2A1	P11166	717
SLC5A2	NR3C2	P08235	715
SLC5A2	MMEL1	Q495T6	697

IntAct

20 interactions, top by confidence:

A	B	Type	Score
SLC5A2	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.580
PDZK1IP1	SLC5A2	psi-mi:“MI:0407”(direct interaction)	0.580
SLC5A2	GAPDHS	psi-mi:“MI:0915”(physical association)	0.560
SLC5A2	GAPDHS	psi-mi:“MI:0914”(association)	0.560
	SLC5A2	psi-mi:“MI:0407”(direct interaction)	0.510
	SLC5A2	psi-mi:“MI:0915”(physical association)	0.510
	SLC5A2	psi-mi:“MI:0915”(physical association)	0.400
SLC5A2		psi-mi:“MI:0915”(physical association)	0.400
	SLC5A2	psi-mi:“MI:0407”(direct interaction)	0.360
PDZK1IP1		psi-mi:“MI:0407”(direct interaction)	0.360
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC5A2	CA2	psi-mi:“MI:0914”(association)	0.350
SLC5A2		psi-mi:“MI:2364”(proximity)	0.270

BioGRID (19): GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), SLC5A2 (Two-hybrid), SLC5A2 (Affinity Capture-MS), SLC5A2 (Affinity Capture-MS), SLC5A2 (Affinity Capture-MS), SLC5A2 (Proximity Label-MS), TUBA3C (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), SLC5A2 (Positive Genetic), SLC5A2 (Co-fractionation), CA2 (Affinity Capture-MS), ERMP1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), SFPQ (Affinity Capture-MS)

ESM2 similar proteins: A0PJK1, A8I1B9, A8WHP3, B9NAE4, D3ZIS0, O02228, O77741, P11170, P13866, P26429, P26430, P31636, P31637, P31639, P41251, P49279, P49280, P53790, P53791, P53792, P53793, P53794, P56436, P70553, P83740, Q27946, Q27981, Q28610, Q28728, Q2M3M2, Q3ZC26, Q5FY69, Q5SWY8, Q6R4Q5, Q7T384, Q8BGY9, Q8C3K6, Q8K0E3, Q8UWF0, Q8VDT1

Diamond homologs: A0PJK1, A8I1B9, A8WHP3, D3ZIS0, P11170, P13866, P26429, P26430, P31636, P31637, P31639, P53790, P53791, P53792, P53793, P53794, P96169, Q28610, Q28728, Q2M3M2, Q3ZC26, Q5FY69, Q5SWY8, Q6R4Q5, Q8C3K6, Q8K0E3, Q8VDT1, Q8WWX8, Q91ZP4, Q923I7, Q9ET37, Q9JKZ2, Q9NY91, Q9Z1F2, P31448

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
canagliflozin	down-regulates	SLC5A2	“chemical inhibition”
dapagliflozin	down-regulates	SLC5A2	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

310 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	25
Uncertain significance	241
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
12904	NM_003041.4(SLC5A2):c.1320G>A (p.Trp440Ter)	Pathogenic
253135	NM_003041.4(SLC5A2):c.265G>A (p.Ala89Thr)	Pathogenic
2577426	NM_003041.4(SLC5A2):c.469-2A>T	Pathogenic
29880	NM_003041.4(SLC5A2):c.127-16C>A	Pathogenic
29881	NM_003041.4(SLC5A2):c.1435C>G (p.Arg479Gly)	Pathogenic
29882	NM_003041.4(SLC5A2):c.294C>A (p.Phe98Leu)	Pathogenic
3066386	NM_003041.4(SLC5A2):c.1499_1506del (p.Leu500fs)	Pathogenic
3256614	NM_003041.4(SLC5A2):c.1665+1del	Pathogenic
3580341	NM_003041.4(SLC5A2):c.1319G>A (p.Trp440Ter)	Pathogenic
4277263	NM_003041.4(SLC5A2):c.1281-1G>A	Pathogenic
4818944	NM_003041.4(SLC5A2):c.617dup (p.Val207fs)	Pathogenic
522538	NM_003041.4(SLC5A2):c.1291del (p.Val431fs)	Pathogenic
1285213	NM_003041.4(SLC5A2):c.1102C>T (p.Arg368Trp)	Likely pathogenic
1297591	NM_003041.4(SLC5A2):c.1280+1G>A	Likely pathogenic
1675620	NM_003041.4(SLC5A2):c.1386C>G (p.Tyr462Ter)	Likely pathogenic
2433567	NM_003041.4(SLC5A2):c.1153_1162del (p.Val385fs)	Likely pathogenic
2632103	NM_003041.4(SLC5A2):c.1593del (p.Ile531fs)	Likely pathogenic
2636558	NM_003041.4(SLC5A2):c.1407del (p.Val470fs)	Likely pathogenic
3256638	NM_003041.4(SLC5A2):c.434T>G (p.Leu145Arg)	Likely pathogenic
3580284	NM_003041.4(SLC5A2):c.333G>A (p.Trp111Ter)	Likely pathogenic
3580288	NM_003041.4(SLC5A2):c.394C>T (p.Arg132Cys)	Likely pathogenic
3580289	NM_003041.4(SLC5A2):c.409C>T (p.Arg137Cys)	Likely pathogenic
3580320	NM_003041.4(SLC5A2):c.962A>G (p.Lys321Arg)	Likely pathogenic
3580326	NM_003041.4(SLC5A2):c.1066G>A (p.Gly356Ser)	Likely pathogenic
3580339	NM_003041.4(SLC5A2):c.1262_1280dup (p.Leu428fs)	Likely pathogenic
3580340	NM_003041.4(SLC5A2):c.1281-2A>G	Likely pathogenic
3580344	NM_003041.4(SLC5A2):c.1361del (p.Asp454fs)	Likely pathogenic
3580347	NM_003041.4(SLC5A2):c.1450-1G>A	Likely pathogenic
3580355	NM_003041.4(SLC5A2):c.1540C>T (p.Pro514Ser)	Likely pathogenic
3580367	NM_003041.4(SLC5A2):c.1711del (p.Glu571fs)	Likely pathogenic

SpliceAI

1989 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31485889:TCTCA:T	donor_gain	1.0000
16:31485890:CTCA:C	donor_gain	1.0000
16:31485891:TCA:T	donor_gain	1.0000
16:31485891:TCAG:T	donor_loss	1.0000
16:31485893:AGTG:A	donor_loss	1.0000
16:31485894:G:GG	donor_gain	1.0000
16:31485894:GTG:G	donor_loss	1.0000
16:31485895:T:A	donor_loss	1.0000
16:31485896:GAGT:G	donor_loss	1.0000
16:31486165:CCAA:C	acceptor_loss	1.0000
16:31486166:CAAGG:C	acceptor_loss	1.0000
16:31486167:A:AG	acceptor_gain	1.0000
16:31486167:AAGGT:A	acceptor_gain	1.0000
16:31486168:A:G	acceptor_gain	1.0000
16:31486286:GGGCT:G	donor_gain	1.0000
16:31486299:G:GT	donor_gain	1.0000
16:31488033:CGTA:C	acceptor_loss	1.0000
16:31488034:GTA:G	acceptor_loss	1.0000
16:31488036:A:C	acceptor_loss	1.0000
16:31488037:G:GC	acceptor_loss	1.0000
16:31488170:CCAG:C	donor_loss	1.0000
16:31488171:CAG:C	donor_loss	1.0000
16:31488172:AGGTA:A	donor_loss	1.0000
16:31488173:GG:G	donor_loss	1.0000
16:31488174:G:GA	donor_loss	1.0000
16:31488175:T:G	donor_loss	1.0000
16:31488377:T:A	acceptor_gain	1.0000
16:31488381:A:AG	acceptor_gain	1.0000
16:31488382:G:GG	acceptor_gain	1.0000
16:31488382:GAC:G	acceptor_gain	1.0000

AlphaMissense

4329 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31488693:A:C	S401R	1.000
16:31488695:C:A	S401R	1.000
16:31488695:C:G	S401R	1.000
16:31484840:A:C	S74R	0.999
16:31484842:C:A	S74R	0.999
16:31484842:C:G	S74R	0.999
16:31484845:C:A	N75K	0.999
16:31484845:C:G	N75K	0.999
16:31484852:A:C	S78R	0.999
16:31484854:T:A	S78R	0.999
16:31484854:T:G	S78R	0.999
16:31486186:G:A	G162E	0.999
16:31487755:A:T	D294V	0.999
16:31488155:A:C	S335R	0.999
16:31488157:C:A	S335R	0.999
16:31488157:C:G	S335R	0.999
16:31488442:T:A	C361S	0.999
16:31488443:G:C	C361S	0.999
16:31488457:T:G	Y366D	0.999
16:31488467:T:C	L369P	0.999
16:31488661:T:C	L390P	0.999
16:31488690:A:C	S400R	0.999
16:31488692:C:A	S400R	0.999
16:31488692:C:G	S400R	0.999
16:31488917:T:A	W440R	0.999
16:31488917:T:C	W440R	0.999
16:31484713:T:C	F56S	0.998
16:31484832:T:A	L71H	0.998
16:31484838:C:A	A73D	0.998
16:31484841:G:T	S74I	0.998

dbSNP variants (sampled 300 via entrez): RS1000316967 (16:31481746 G>A), RS1000598313 (16:31490618 A>C,G), RS1000795934 (16:31488900 T>A,C), RS1000950348 (16:31483349 G>A), RS1001032547 (16:31487137 C>T), RS1001101811 (16:31481417 C>T), RS1001127045 (16:31487364 G>A,T), RS1001130758 (16:31483558 A>G), RS1001583744 (16:31486491 T>A), RS1001591878 (16:31486662 T>G), RS1001821063 (16:31487392 T>C), RS1002402878 (16:31481970 A>C,T), RS1002497698 (16:31482409 G>C), RS1003723104 (16:31485345 T>A,C), RS1003905773 (16:31482422 G>A)

Disease associations

OMIM: gene MIM:182381 | disease phenotypes: MIM:233100, MIM:612286

GenCC curated gene-disease

Disease	Classification	Inheritance
familial renal glucosuria	Definitive	Autosomal recessive

Mondo (3): familial renal glucosuria (MONDO:0009297), prostate cancer (MONDO:0008315), hypophosphatemic nephrolithiasis/osteoporosis 1 (MONDO:0012850)

Orphanet (3): Familial renal glucosuria (Orphanet:69076), Familial prostate cancer (Orphanet:1331), Dominant hypophosphatemia with nephrolithiasis or osteoporosis (Orphanet:244305)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000103	Polyuria
HP:0000112	Nephropathy
HP:0000124	Renal tubular dysfunction
HP:0000805	Enuresis
HP:0000855	Insulin resistance
HP:0001944	Dehydration
HP:0001946	Ketosis
HP:0001959	Polydipsia
HP:0002591	Polyphagia
HP:0003074	Hyperglycemia
HP:0003076	Glycosuria
HP:0003828	Variable expressivity
HP:0004924	Abnormal oral glucose tolerance
HP:0008855	Moderate postnatal growth retardation
HP:0010677	Enuresis nocturna
HP:0040214	Abnormal circulating insulin concentration
HP:0040217	Elevated hemoglobin A1c

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST008605_1	Glucosuria (moderate to severe)	1.000000e-11
GCST008605_4	Glucosuria (moderate to severe)	1.000000e-09
GCST008606_1	Glucosuria (mild)	6.000000e-09
GCST008606_3	Glucosuria (mild)	9.000000e-12
GCST008614_1	Glucosuria	2.000000e-13
GCST008614_5	Glucosuria	4.000000e-13
GCST008614_6	Glucosuria	5.000000e-15

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006030	Glycosuria, Renal	C12.050.351.968.419.815.532; C12.050.351.968.934.363.450; C12.200.777.419.815.532; C12.200.777.934.363.450; C12.950.419.815.532; C12.950.934.363.450; C16.320.831.532; C18.452.394.937.450
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C567363	Nephrolithiasis-Osteoporosis, Hypophosphatemic, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3884 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,484 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1770248	ERTUGLIFLOZIN	4	1,857
CHEMBL1808388	BEXAGLIFLOZIN	4	463
CHEMBL2018096	IPRAGLIFLOZIN	4	2,101
CHEMBL2048484	CANAGLIFLOZIN ANHYDROUS	4	4,237
CHEMBL2105711	TOFOGLIFLOZIN	4	135
CHEMBL2107830	EMPAGLIFLOZIN	4	3,982
CHEMBL2110731	TOFOGLIFLOZIN ANHYDROUS	4	1,556
CHEMBL3039507	SOTAGLIFLOZIN	4	1,661
CHEMBL429910	DAPAGLIFLOZIN	4	5,323
CHEMBL3703921	ENAVOGLIFLOZIN	3	147
CHEMBL4297431	HENAGLIFLOZIN	3	140
CHEMBL1093423	LUSEOGLIFLOZIN	2	1,189
CHEMBL2028665	REMOGLIFLOZIN ETABONATE	2	944
CHEMBL2397450	YM-543 FREE ACID	2	181
CHEMBL4297625	LICOGLIFLOZIN	2	513
CHEMBL450044	SERGLIFLOZIN ETABONATE	2	1,055

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9924771	SLC5A2		0.00	0
rs11646054	SLC5A2		0.00	0
rs3116149	SLC5A2		0.00	0
rs3116150	SLC5A2		0.00	0
rs3813008	SLC5A2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Hexose transporter family

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
licogliflozin	Inhibition	9.3	pIC50
dapagliflozin	Inhibition	9.3	pIC50
enavogliflozin	Inhibition	9.1	pIC50
ertugliflozin	Inhibition	9.06	pIC50
sotagliflozin	Inhibition	8.74	pIC50
bexagliflozin	Inhibition	8.64	pIC50
janagliflozin	Inhibition	8.6	pIC50
tofogliflozin	Inhibition	8.54	pIC50
empagliflozin	Inhibition	8.5	pIC50
canagliflozin	Inhibition	8.4	pIC50
ipragliflozin	Inhibition	8.13	pIC50
remogliflozin	Inhibition	7.9	pKi
sergliflozin	Inhibition	6.8	pKi

Binding affinities (BindingDB)

542 measured of 649 human assays (649 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,3R,4R,5S,6R)-2-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-methylphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.105 nM	US-20250129055
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]-5-methoxyphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.308 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[3-(3,4-dihydro-2H-chromen-6-ylmethyl)-4-methylphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.356 nM	US-20250129055
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-cyclopropylphenyl)methyl]-1,3-benzodioxol-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.366 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethenylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.366 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethylphenyl)methyl]-1,3-benzodioxol-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.404 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-hydroxyphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.454 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-cyclopropylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.463 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[[4-(dimethylamino)phenyl]methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.475 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-methoxyphenyl)methyl]-2-prop-2-enoxyphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.504 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethoxyphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.551 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-5-methoxyphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.551 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[8-chloro-7-[(4-methoxyphenyl)methyl]-3,4-dihydro-2H-thiochromen-5-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.552 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-prop-1-en-2-ylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.574 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(1S,2S,3S,4R,5S)-5-[4-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol	IC50	0.58 nM	US-10011627: C-aryl glucoside derivative, preparation methods thereof, and medical applications thereof
(2S,3R,4R,5S,6R)-2-[7-chloro-6-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.616 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethylphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.627 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-methoxyphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.628 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)phenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.629 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[5-chloro-6-[(4-cyclopropylphenyl)methyl]-2,3-dihydro-1,4-benzodioxin-8-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.651 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-bromo-6-[(4-ethylphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.661 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-cyclopropylphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.678 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-methoxyphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.681 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethoxyphenyl)methyl]-2-methyl-2,3-dihydro-1-benzofuran-7-yl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.685 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethylphenyl)methyl]-2-methyl-2,3-dihydro-1-benzofuran-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.706 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.715 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-(difluoromethyl)-6-[(4-ethylphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.718 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethylphenyl)methyl]-3-methyl-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.721 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4S,5S,6R)-2-[7-chloro-6-[(4-ethoxyphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-methyloxane-3,4,5-triol	IC50	0.728 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-(difluoromethyl)-6-[(4-methoxyphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.734 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-bromo-6-[(4-ethoxyphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.738 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethenylphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.742 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[8-chloro-7-[(4-ethylphenyl)methyl]-3,4-dihydro-2H-chromen-5-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.753 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
CHEMBL1819199	IC50	0.778 nM	US-8921412: C-aryl ansa SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethoxyphenyl)methyl]-2-methoxyphenyl]-6-methylsulfanyloxane-3,4,5-triol	IC50	0.783 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[3-(1,4-benzodioxin-6-ylmethyl)-4-chlorophenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.788 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-propan-2-ylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.794 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-methylphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.808 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethoxyphenyl)methyl]-2,3-dihydro-1-benzofuran-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.833 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethylphenyl)methyl]-2-methyl-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.835 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[5-chloro-6-[(4-ethylphenyl)methyl]-3,4-dihydro-2H-chromen-8-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.845 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[5-chloro-6-[(4-cyclopropylphenyl)methyl]-3,4-dihydro-2H-chromen-8-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.851 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[6-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-7-methyl-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.86 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[3-(1-benzothiophen-5-ylmethyl)-4-chlorophenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.865 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethoxyphenyl)methyl]-3-methyl-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.867 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-propan-2-ylphenyl)methyl]-1,3-benzodioxol-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.872 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[8-chloro-7-[(4-cyclopropylphenyl)methyl]-3,4-dihydro-2H-chromen-5-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.881 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethylphenyl)methyl]-2,3-dihydro-1-benzofuran-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.884 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-2-methyl-5-[(4-propylphenyl)methyl]-2,3-dihydro-1-benzofuran-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.885 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethylphenyl)methyl]-3-methyl-2,3-dihydro-1-benzofuran-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.891 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors

ChEMBL bioactivities

2262 potent at pChembl≥5 of 2326 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL565781
9.52	IC50	0.3	nM	CHEMBL1164052
9.51	IC50	0.308	nM	CHEMBL3703868
9.46	IC50	0.35	nM	CHEMBL5288495
9.44	IC50	0.366	nM	CHEMBL3703908
9.44	IC50	0.366	nM	CHEMBL3703920
9.43	IC50	0.37	nM	CHEMBL3703908
9.43	IC50	0.37	nM	CHEMBL3703920
9.40	IC50	0.4	nM	CHEMBL3703912
9.39	IC50	0.404	nM	CHEMBL3703912
9.36	IC50	0.44	nM	CHEMBL3703785
9.34	IC50	0.454	nM	CHEMBL3703855
9.34	IC50	0.46	nM	ENAVOGLIFLOZIN
9.33	IC50	0.463	nM	ENAVOGLIFLOZIN
9.33	IC50	0.47	nM	CHEMBL4114400
9.32	IC50	0.475	nM	CHEMBL3703870
9.31	IC50	0.49	nM	CHEMBL4112174
9.31	IC50	0.49	nM	CHEMBL4111780
9.31	IC50	0.49	nM	DAPAGLIFLOZIN
9.30	IC50	0.504	nM	CHEMBL3703864
9.30	IC50	0.5	nM	CHEMBL4113334
9.30	IC50	0.5	nM	LICOGLIFLOZIN
9.26	IC50	0.551	nM	CHEMBL3703792
9.26	IC50	0.551	nM	CHEMBL3703867
9.26	IC50	0.552	nM	CHEMBL3654936
9.26	IC50	0.55	nM	CHEMBL3703792
9.26	IC50	0.55	nM	CHEMBL3654936
9.24	IC50	0.574	nM	CHEMBL3703929
9.23	IC50	0.59	nM	CHEMBL4114272
9.22	IC50	0.6	nM	CHEMBL4108764
9.21	IC50	0.616	nM	CHEMBL3703861
9.21	IC50	0.61	nM	CHEMBL3703788
9.21	IC50	0.62	nM	CHEMBL4114842
9.20	IC50	0.629	nM	CHEMBL3703848
9.20	IC50	0.628	nM	CHEMBL3703852
9.20	IC50	0.627	nM	CHEMBL3654932
9.20	IC50	0.63	nM	CHEMBL3654932
9.20	IC50	0.63	nM	CHEMBL4126863
9.19	IC50	0.651	nM	CHEMBL3703913
9.19	IC50	0.65	nM	CHEMBL3703913
9.18	IC50	0.661	nM	CHEMBL3703788
9.17	IC50	0.67	nM	CHEMBL3125150
9.17	IC50	0.681	nM	CHEMBL3703789
9.17	IC50	0.678	nM	CHEMBL3703872
9.17	IC50	0.68	nM	CHEMBL3703789
9.17	IC50	0.67	nM	CHEMBL4110395
9.17	IC50	0.67	nM	CHEMBL3891805
9.16	IC50	0.685	nM	CHEMBL3703898
9.16	IC50	0.69	nM	CHEMBL3703898

PubChem BioAssay actives

1226 with measured affinity, of 1560 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethylphenyl)methyl]-2-(prop-2-ynoxymethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	487637: Inhibition of human SGLT2 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 1.5 hrs by liquid scintillation counting	ic50	0.0003	uM
(3S,3’R,4’S,5’S,6’R)-6-chloro-6’-(hydroxymethyl)-5-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,2’-oxane]-3’,4’,5’-triol	444172: Inhibition of human SGLT2 transfected in HEK293.ETN cells assessed as AMG uptake after 1.5 hrs by scintillation counting	ic50	0.0003	uM
(2S,3R,4R,6R)-2-[4-chloro-3-[(4-ethylphenyl)methyl]phenyl]-5,5-difluoro-6-(hydroxymethyl)oxane-3,4-diol	1954238: Inhibition of human SGLT2	ic50	0.0003	uM
(2S,3R,4R,5S,6R)-2-[7-bromo-6-[(4-methoxyphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0004	uM
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethenylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0004	uM
(2S,3R,4R,5S,6R)-2-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-ethylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1721968: Inhibition of SGLT2 (unknown origin)	ic50	0.0005	uM
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-cyclopropylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0005	uM
Dapagliflozin	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0005	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethylphenyl)methyl]-2-hydroxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1496228: Inhibition of full-length human SGLT2 expressed in CHO cells assessed as decrease in [14C]-methyl alpha-D-glucopyranoside uptake after 1 hr by liquid scintillation counting method	ic50	0.0006	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[5-(furan-2-yl)-1,3-thiazol-2-yl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	570205: Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting	ic50	0.0007	uM
(2S,3R,4S,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methyloxane-3,4,5-triol	1076412: Inhibition of human SGLT2	ic50	0.0007	uM
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-ethylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0007	uM
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-methoxyphenyl)methyl]-2,3-dihydro-1H-inden-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0007	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-2-hydroxy-5-[(4-methylphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1496228: Inhibition of full-length human SGLT2 expressed in CHO cells assessed as decrease in [14C]-methyl alpha-D-glucopyranoside uptake after 1 hr by liquid scintillation counting method	ic50	0.0008	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[dideuterio-[4-(trideuteriomethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1075135: Inhibition of full length human SGLT2 assessed as methyl-alpha-D-[U-14C]glucopyranoside uptake after 1.5 hrs by cell-based topcount scintillation counting analysis	ic50	0.0008	uM
(3S,3’R,4’S,5’S,6’R)-6-chloro-5-[(2-fluoro-3-methylphenyl)methyl]-6’-(hydroxymethyl)spiro[1H-2-benzofuran-3,2’-oxane]-3’,4’,5’-triol	444172: Inhibition of human SGLT2 transfected in HEK293.ETN cells assessed as AMG uptake after 1.5 hrs by scintillation counting	ic50	0.0008	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(5-thiophen-3-yl-1,3-thiazol-2-yl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	570205: Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting	ic50	0.0008	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[[5-(furan-2-yl)-1,3-thiazol-2-yl]methyl]-2-hydroxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	601552: Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counter	ic50	0.0008	uM
(1S,16R,17S,18R,19R)-5-chloro-4-[(4-methylsulfanylphenyl)methyl]-8,14,20-trioxatricyclo[14.3.1.02,7]icosa-2(7),3,5-triene-17,18,19-triol	614528: Inhibition of human SGLT2 expressed in CHO cells assessed as reduction of [14C]-labeled AMG after 2 hrs by liquid scintillation counting	ic50	0.0008	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(5-pyridin-3-ylthiophen-2-yl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	763800: Inhibition of human SGLT2 expressed in CHOK cells assessed as reduction of [14C]alpha-methyl-D-glucopyranoside uptake after 120 mins by liquid scintillation counting	ic50	0.0008	uM
(2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-[6-[(4-methoxyphenyl)methyl]-7-methyl-2,3-dihydro-1H-inden-4-yl]oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0008	uM
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-propan-2-ylphenyl)methyl]-2,3-dihydro-1-benzofuran-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0008	uM
Ertugliflozin	1413443: Inhibition of SGLT2 (unknown origin)	ic50	0.0009	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethylphenyl)methyl]-2-(methoxymethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	487637: Inhibition of human SGLT2 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 1.5 hrs by liquid scintillation counting	ic50	0.0009	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethoxyphenyl)methyl]-2-(2-methoxyethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	487637: Inhibition of human SGLT2 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 1.5 hrs by liquid scintillation counting	ic50	0.0009	uM
(1S,2S,3S,4R,5S)-5-[4-chloro-3-[(4-methoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol	595066: Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of methyl alpha-D-glucopyranoside uptake after 1 hr	ic50	0.0009	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-2-prop-2-enoxy-5-[(5-thiophen-3-yl-1,3-thiazol-2-yl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	601552: Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counter	ic50	0.0009	uM
(1S,16R,17S,18R,19R)-5-chloro-4-[(4-ethoxyphenyl)methyl]-8,14,20-trioxatricyclo[14.3.1.02,7]icosa-2(7),3,5-triene-17,18,19-triol	614528: Inhibition of human SGLT2 expressed in CHO cells assessed as reduction of [14C]-labeled AMG after 2 hrs by liquid scintillation counting	ic50	0.0009	uM
4-[4-[[2-chloro-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenoxy]-N-(1-hydroxy-2-methylpropan-2-yl)butanamide	1436423: Inhibition of human HA-tagged SGLT2 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0009	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-2-hydroxy-4-methoxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-ethyl-2-methoxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-2,4-dimethoxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[3-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-methylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[3-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-chlorophenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-2-hydroxy-4-methylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-chloro-2-hydroxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-2-methoxy-4-methylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-chloro-2-methoxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390387: Inhibition of human kidney SGLT2 expressed in CHOK1 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by TopCount method	ic50	0.0010	uM
(1R,2S,3R,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(difluoromethoxy)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol	1447831: Inhibition of human SGLT2 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-ethoxyphenyl)methyl]-2-hydroxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1496228: Inhibition of full-length human SGLT2 expressed in CHO cells assessed as decrease in [14C]-methyl alpha-D-glucopyranoside uptake after 1 hr by liquid scintillation counting method	ic50	0.0010	uM
(1S,10Z,15R,16S,17R,18R)-5-chloro-4-[(4-ethoxyphenyl)methyl]-8,13,19-trioxatricyclo[13.3.1.02,7]nonadeca-2(7),3,5,10-tetraene-16,17,18-triol	614528: Inhibition of human SGLT2 expressed in CHO cells assessed as reduction of [14C]-labeled AMG after 2 hrs by liquid scintillation counting	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[5-chloro-6-[(4-methoxyphenyl)methyl]-3,4-dihydro-2H-chromen-8-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1888489: Inhibition of human SGLT2 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0010	uM
(2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-[4-methyl-3-[(5-pyridin-3-ylthiophen-2-yl)methyl]phenyl]oxane-3,4,5-triol	763800: Inhibition of human SGLT2 expressed in CHOK cells assessed as reduction of [14C]alpha-methyl-D-glucopyranoside uptake after 120 mins by liquid scintillation counting	ic50	0.0010	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-methoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	466464: Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent methyl-alpha-D-[U-14C]glucopyranoside uptake after 2 hrs	ic50	0.0010	uM
2-[[(1S,2S,3R,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2,3,4-trihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl]oxy]acetonitrile	1447831: Inhibition of human SGLT2 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method	ic50	0.0011	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-2-hydroxy-5-[(4-methoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1496228: Inhibition of full-length human SGLT2 expressed in CHO cells assessed as decrease in [14C]-methyl alpha-D-glucopyranoside uptake after 1 hr by liquid scintillation counting method	ic50	0.0011	uM
(2S,3R,4R,6R)-2-[4-chloro-2-hydroxy-5-[(4-methoxyphenyl)methyl]phenyl]-5,5-difluoro-6-(hydroxymethyl)oxane-3,4-diol	1721933: Inhibition of human SGLT2 expressed in CHO cells assessed as reduction in [14C]-methyl-alpha -D-glucopyranoside accumulation	ic50	0.0011	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(2-thiophen-3-yl-1,3-thiazol-5-yl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	570205: Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting	ic50	0.0011	uM
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(5-thiophen-2-yl-1,3-thiazol-2-yl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	570205: Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting	ic50	0.0011	uM
(1S,2S,3S,4R,5S)-1-(hydroxymethyl)-5-[3-[(4-methoxyphenyl)methyl]-4-methylphenyl]-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol	595066: Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of methyl alpha-D-glucopyranoside uptake after 1 hr	ic50	0.0011	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Bexagliflozin	decreases activity	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
T 1095	decreases activity	1
sergliflozin	decreases activity	1
dapagliflozin	decreases activity	1
remogliflozin etabonate	decreases activity	1
jinfukang	affects cotreatment, decreases expression	1
4-chloro-3-(4-cyclopropylbenzyl)-1-(xylopyranosyl)-1H-indole	decreases activity	1
ertugliflozin	decreases activity	1
Canagliflozin	decreases activity	1
Sorafenib	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phlorhizin	decreases activity	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

160 unique, capped per target: 157 binding, 2 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005353	Binding	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]alpha-methyl-D-glucopyranoside uptake by fluorescence polarization assay	Design and synthesis of fluorescent SGLT2 inhibitors. — Bioorg Med Chem Lett
CHEMBL4003746	ADMET	Inhibition of human HA-tagged SGLT2 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	Discovery of LX2761, a Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitor Restricted to the Intestinal Lumen, for the Treatment of Diabetes. — J Med Chem
CHEMBL5723517	Functional	Affinity On-target Cellular interaction: (AMG uptake assay in presence of 25% human plasma, 293.ETN cells) EUB0002515a SLC5A2	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TN96	HAP1 SLC5A2 (-) 1	Cancer cell line	Male
CVCL_TN97	HAP1 SLC5A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer