SLC5A1

Summary

SLC5A1 (solute carrier family 5 member 1, HGNC:11036) is a protein-coding gene on chromosome 22q12.3, encoding Sodium/glucose cotransporter 1 (P13866). Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.

This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6523 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glucose-galactose malabsorption (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 551 total — 20 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11036
Approved symbol	SLC5A1
Name	solute carrier family 5 member 1
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	D22S675, NAGT, SGLT-1
Ensembl gene	ENSG00000100170
Ensembl biotype	protein_coding
OMIM	182380
Entrez	6523

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000266088, ENST00000477969, ENST00000486394, ENST00000543737, ENST00000878506

RefSeq mRNA: 2 — MANE Select: NM_000343 NM_000343, NM_001256314

CCDS: CCDS13902, CCDS58805

Canonical transcript exons

ENST00000266088 — 15 exons

Exon	Start	End
ENSE00001296527	32049943	32050014
ENSE00001301239	32043261	32043416
ENSE00001305219	32104786	32104891
ENSE00001310820	32102022	32102237
ENSE00001327082	32109990	32113029
ENSE00001679729	32081866	32081971
ENSE00001692331	32083074	32083154
ENSE00003461665	32099183	32099351
ENSE00003478588	32068496	32068600
ENSE00003513761	32066935	32067039
ENSE00003557974	32084439	32084659
ENSE00003564125	32067967	32068026
ENSE00003631397	32084900	32085035
ENSE00003671642	32086220	32086327
ENSE00003691577	32091612	32091762

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 98.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.0395 / max 2398.1754, expressed in 75 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191859	2.4736	25
191856	0.4008	46
191857	0.0574	27
191858	0.0435	21
191861	0.0314	11
191855	0.0261	12
209454	0.0068	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.97	gold quality
ileal mucosa	UBERON:0000331	98.91	gold quality
duodenum	UBERON:0002114	95.72	gold quality
apex of heart	UBERON:0002098	94.62	gold quality
heart left ventricle	UBERON:0002084	93.87	gold quality
cardiac ventricle	UBERON:0002082	93.60	gold quality
gall bladder	UBERON:0002110	93.13	gold quality
heart right ventricle	UBERON:0002080	90.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.60	gold quality
right atrium auricular region	UBERON:0006631	90.60	gold quality
small intestine	UBERON:0002108	89.75	gold quality
cardiac atrium	UBERON:0002081	89.39	gold quality
left ventricle myocardium	UBERON:0006566	87.98	gold quality
pancreatic ductal cell	CL:0002079	86.32	silver quality
heart	UBERON:0000948	85.97	gold quality
myocardium	UBERON:0002349	83.51	silver quality
skin of abdomen	UBERON:0001416	83.41	gold quality
islet of Langerhans	UBERON:0000006	83.00	gold quality
skin of leg	UBERON:0001511	83.00	gold quality
minor salivary gland	UBERON:0001830	82.90	gold quality
rectum	UBERON:0001052	82.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.02	silver quality
lower esophagus mucosa	UBERON:0035834	80.75	gold quality
mouth mucosa	UBERON:0003729	80.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.09	gold quality
zone of skin	UBERON:0000014	79.78	gold quality
saliva-secreting gland	UBERON:0001044	78.57	gold quality
gingiva	UBERON:0001828	76.57	gold quality
epithelial cell of pancreas	CL:0000083	76.22	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	76.00	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	690.49
E-ANND-3	yes	16.74
E-MTAB-6386	no	7.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, GATA5, HNF1A, HNF1B, NR3C1, PER1, PGR, SP1

miRNA regulators (miRDB)

90 targeting SLC5A1, 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-4673	100.00	66.64	1490
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4465	99.71	72.56	2096

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutations of this gene protein (mapped to Chromosome 22) causes glucose-galactose malabsorption in infants. Sugar transport is impaired mainly because the mutant proteins are either truncated or are not targeted properly to the cell membrane. (PMID:12139397)
• Intracellular compartments containing SGLT1 are involved in the regulation of SGLT1 abundance at the apical cell surface. (PMID:12773314)
• Taken together, these data indicate that RSC1A1 modulates dynamin-dependent trafficking of intracellular vesicles containing hSGLT1 in Xenopus oocytes, and modulates PKC-dependent short-term regulation of this transporter. (PMID:14724758)
• Na+-coupled glucose transporter 1 (SGLT1) was regulated by neuronal cell expressed developmentally downregulated 4-2 (Nedd4-2) and serum- and glucocorticoid-inducible kinase 1 (SGK1) (PMID:15166308)
• Aspartate residue 454 of SGLT1 is critically important for normal trafficking of the protein to the plasma membrane. (PMID:15476411)
• Our results indicate that the major voltage-dependent step of the Na(+)/glucose transport cycle is the return of the empty carrier from inward to outward facing conformations. (PMID:15596535)
• Thus, the C351A and C361A mutations might cause a global reorganization of the disulfide bonds of SGLT1. (PMID:15885653)
• the large, hydrophilic loop near the carboxyl terminus of SGLT1 does not appear to play a major part in the binding of phlorizin (PMID:15904891)
• SGLT-1 has a role in glucose uptake and in protecting intestinal epithelial cells against LPS-induced apoptosis and barrier defects (PMID:16260652)
• 3 conformational states of SGLT1 differ in their packing density and surface hydrophobicity, reflecting the empty carrier, the d-glucose loaded carrier facing the outside of membrane and the complex of the outside-orientated carrier with phlorizin (PMID:16300400)
• water transport across the membrane can be explained by cotransport of water in the membrane proteins and that intracellular unstirred layers effects are minute (PMID:16322051)
• results indicate that cysteine residues C255 and C511 form a disulfide bridge in human SGLT1 and that this disulfide bridge is involved in the conformational change of the free carrier (PMID:16446504)
• hRS1 protein exhibits glucose-dependent, short-term inhibition of hSGLT1 and hOCT2 by inhibiting the release of vesicles from the trans-Golgi network. (PMID:16788146)
• description of a novel feedback mechanism in apoptotic signaling pathway for SGLT-1-dependent cytoprotection; observation suggests new function for CD14 on enterocytes involving induction of caspase-dependent SGLT-1 activity which leads to cell rescue (PMID:16860318)
• study examines the conformations of the Na(+)/glucose cotransporter during sugar transport using charge and fluorescence measurements (PMID:17130520)
• Results describe the effect of taurine on glucose transporter using heterologous expression of sodium-glucose transporter-1 (SGLT-1). (PMID:17153597)
• These studies demonstrate the existence of different conformational states of the membrane-embedded transporter in its glucose-free form, as sodium-glucose-carrier complex and as sodium-phlorizin-carrier complex. (PMID:17222499)
• Thioglycoside VII (2-hydroxymethyl-phenyl-1’-thio-beta-D-galacto-pyranoside) had a pronounced inhibitory effect on hSGLT1. (PMID:17505558)
• RSC1A1 codes for a 67-kDa protein named RS1 that mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. (PMID:17686765)
• D28G mutation in 16 family members of a patient with typical presentation of congenital glucose-galactose malabsorption (PMID:17903058)
• the native carrier ( sodium/D-glucose cotransporter 1)residues Gln at position 457 and Thr at position 460 reside in a hydrophilic access pathway extending 5-7 A into the membrane to which sugars as well as the sugar moiety of inhibitory glucosides bind (PMID:17983207)
• this high-capacity functional assay should provide a means to identify novel and selective SGLT inhibitors (PMID:18471079)
• Ongoing work is aimed at identifying the localization signals in the SGLT1 3’-UTR and the corresponding binding proteins. (PMID:18481997)
• activation of SGLT-1 by glucose protects from damages induced by TLR ligands, in human intestinal epithelial cells and in a murine model of septic shock. (PMID:18713983)
• High SGLT1 expression in pancreatic adenocarcinomas significantly correlates with DFS & a trend was found for OS, especially in younger patients. High SGLT1 expression in primary tumors correlates with high Bcl-2 expression, not p53 expression. (PMID:18853313)
• Protein kinase A-mediated phosphorylation of the transporter represents a further mechanism in the regulation of SGLT1-mediated glucose transport in epithelial cells (PMID:19115253)
• cardiac SGLT1 expression and/or function are regulated by insulin and leptin, and are perturbed in disease. (PMID:19509029)
• These observations support a role for AMPK in the regulation of Na+-coupled glucose transport. (PMID:20334581)
• This study indicates that the leak current associated with SGLT1 is mediated by a variety of monovalent cations, including cations that do not generate the conformational changes associated to the Na+ binding site used for cotransport. (PMID:20338844)
• Glucose-galactose malabsorption is life-threatening newborn diarrhea caused by mutations in the Na(+) /glucose cotransporter gene SLC5A1 that described herein. (PMID:20486940)
• Polyphenols, phenolic acids and tannins from strawberry and apple are potent inhibitors of GLUT2 and SGLT1 at concentrations predicted after dietary ingestion. (PMID:20564476)
• 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)
• Expression of SGLT1 and EGFR in colorectal cancer tissues was higher than that in normal tissues and their expression related with clinical stage. (PMID:21080109)
• HPV18 E6 oncoprotein participates in the upregulation of SGLT1. (PMID:21156162)
• An independent estimation of the turnover rate for human SGLT1 expressed in Xenopus laevis oocytes, was obtained applying the ion-trap technique. (PMID:21190656)
• JAK2 upregulates SGLT1 activity which may play a role in the effect of JAK2 during ischemia and malignancy. (PMID:21406183)
• the structural basis of cotransporter water permeability (PMID:22004742)
• Data suggest that “gate” residues in SGLT1 contribute directly to the coupling between substrate and Na+ transport (PMID:22159082)
• SGLT1 overexpression, as examined by immunohistochemistry, is an independent biomarker for poor prognosis of patients with ovarian carcinoma. (PMID:22159627)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc5a1	ENSDARG00000013871
mus_musculus	Slc5a1	ENSMUSG00000011034
rattus_norvegicus	Slc5a1	ENSRNOG00000017775
drosophila_melanogaster	CG2187	FBGN0017448
drosophila_melanogaster	rumpel	FBGN0029950
drosophila_melanogaster	SLC5A11	FBGN0031998
drosophila_melanogaster	bumpel	FBGN0037895
drosophila_melanogaster	salt	FBGN0039872
drosophila_melanogaster	Smvt	FBGN0039873
drosophila_melanogaster	CG31262	FBGN0051262
drosophila_melanogaster	CG31668	FBGN0051668
drosophila_melanogaster	CG33124	FBGN0053124
drosophila_melanogaster	kumpel	FBGN0250757

Paralogs (12): SLC5A4 (ENSG00000100191), SLC5A5 (ENSG00000105641), SLC5A7 (ENSG00000115665), SLC5A9 (ENSG00000117834), SLC5A6 (ENSG00000138074), SLC5A2 (ENSG00000140675), SLC5A12 (ENSG00000148942), SLC5A10 (ENSG00000154025), SLC5A11 (ENSG00000158865), SLC5A3 (ENSG00000198743), SLC5A8 (ENSG00000256870), (ENSG00000293606)

Protein

Protein identifiers

Sodium/glucose cotransporter 1 — P13866 (reviewed: P13866)

Alternative names: High affinity sodium-glucose cotransporter, Solute carrier family 5 member 1

All UniProt accessions (1): P13866

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Has a primary role in the transport of dietary monosaccharides from enterocytes to blood. Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2. Additionally, functions as a D-glucose sensor in enteroendocrine cells, triggering the secretion of the incretins GCG and GIP that control food intake and energy homeostasis. Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules. Transports D-glucose into endometrial epithelial cells, controlling glycogen synthesis and nutritional support for the embryo as well as the decidual transformation of endometrium prior to conception. Acts as a water channel enabling passive water transport across the plasma membrane in response to the osmotic gradient created upon sugar and Na(+) uptake. Has high water conductivity, comparable to aquaporins, and therefore is expected to play an important role in transepithelial water permeability, especially in the small intestine.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed in intestine. Expressed in endometrial cells.

Post-translational modifications. N-glycosylation is not necessary for the cotransporter function.

Disease relevance. Congenital glucose/galactose malabsorption (GGM) [MIM:606824] Intestinal monosaccharide transporter deficiency. It is an autosomal recessive disorder manifesting itself within the first weeks of life. It is characterized by severe diarrhea and dehydration which are usually fatal unless glucose and galactose are eliminated from the diet. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Enhanced by the interaction with PDZK1IP1/MAP17; but unlike SLC5A2/SGLT2, PDZK1IP1 is not essential for SLC5A1 transporter activity. Inhibited by phlorizin. Possibly modulated by cholesterol binding.

Domain organisation. The cholesterol-binding site is formed by transmembrane helices TM1, TM7 and TM13.

Induction. Up-regulated upon transition of the endometrium from the non-receptive early secretory phase to the receptive mid-secretory phase of the cycle.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P13866-1	1	yes
P13866-2	2

RefSeq proteins (2): NP_000334, NP_001243243 (=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), 2 shown:

• D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in) (RHEA:70495)
• D-galactose(out) + 2 Na(+)(out) = D-galactose(in) + 2 Na(+)(in) (RHEA:70499)

UniProt features (144 total): helix 35, sequence variant 25, mutagenesis site 23, topological domain 15, transmembrane region 14, turn 11, strand 7, disulfide bond 5, site 3, chain 1, binding site 1, modified residue 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7SLA	ELECTRON MICROSCOPY	3.15
7WMV	ELECTRON MICROSCOPY	3.2
7YNI	ELECTRON MICROSCOPY	3.26
7SL8	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13866-F1	84.53	0.53

Antibody-complex structures (SAbDab): 2 — 7SL8, 7SLA

Functional residue map

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

Catalytic / active sites (3): 43 (implicated in sodium coupling); 300 (implicated in sodium coupling); 460 (involved in sugar-binding/transport and inhibitor binding)

Ligand- & substrate-binding residues (1): 457

Post-translational modifications (1): 587

Disulfide bonds (5): 255–610, 255–511, 345–351, 355–361, 517–522

Glycosylation sites (1): 248

Mutagenesis-validated functional residues (23):

Position	Phenotype
67	strong reduction in d-glucose transporter activity.
77	loss of activity.
83	acquires d-mannose, d-fructose and l-sorbose transporter activity; when associated with a-287 and c-290.
83	loss of d-glucose transporter activity.
204	loss of activity.
248	loss of n-glycosylation.
287	acquires d-mannose, d-fructose and l-sorbose transporter activity; when associated with l-83 and c-290.
287	loss of d-glucose transporter activity. has strict selectivity for d-galactose.
287	has normal d-glucose and d-galactose transporter activity.
290	loss of d-galactose transporter activity. has strict selectivity for d-glucose. acquires d-mannose, d-fructose and l-sor
291	loss of d-glucose transporter activity.
292	has no effect on water permeability.
321	acquires d-mannose and d-allose transporter activity comparable to glucose and galactose.
363	loss of water permeation.
396	loss of activity.
451	strong reduction in water permeation.
452	loss of water permeation.
454	has no effect on water permeation.
457	loss of d-glucose transporter activity.
457	strong reduction in d-glucose transporter activity.
460	loss of d-glucose transporter activity.
641	slightly reduced d-glucose transporter activity.
660–661	loss of d-glucose transporter activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-5656364	Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM)
R-HSA-8981373	Intestinal hexose absorption
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
R-HSA-8963676	Intestinal absorption
R-HSA-8963743	Digestion and absorption

MSigDB gene sets: 226 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_DIGESTION, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, HNF1_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_WATER_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, MODULE_480, GOBP_TRANSEPITHELIAL_TRANSPORT, GOBP_DIGESTIVE_SYSTEM_PROCESS, SANSOM_APC_TARGETS_DN

GO Biological Process (16): alpha-glucoside transport (GO:0000017), intestinal D-glucose absorption (GO:0001951), sodium ion transport (GO:0006814), pentose transmembrane transport (GO:0015750), fucose transmembrane transport (GO:0015756), galactose transmembrane transport (GO:0015757), myo-inositol transport (GO:0015798), transepithelial water transport (GO:0035377), renal D-glucose absorption (GO:0035623), D-glucose import across plasma membrane (GO:0098708), sodium ion import across plasma membrane (GO:0098719), intestinal hexose absorption (GO:0106001), transport across blood-brain barrier (GO:0150104), D-glucose transmembrane transport (GO:1904659), monoatomic ion transport (GO:0006811), transmembrane transport (GO:0055085)

GO Molecular Function (13): galactose transmembrane transporter activity (GO:0005354), myo-inositol:sodium symporter activity (GO:0005367), water transmembrane transporter activity (GO:0005372), D-glucose:sodium symporter activity (GO:0005412), pentose transmembrane transporter activity (GO:0015146), fucose transmembrane transporter activity (GO:0015150), alpha-glucoside transmembrane transporter activity (GO:0015151), galactose:sodium symporter activity (GO:0015371), 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 (10): early endosome (GO:0005769), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), nuclear membrane (GO:0031965), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), intracellular vesicle (GO:0097708), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hexose transmembrane transport	3
hexose transmembrane transporter activity	3
solute:sodium symporter activity	3
water transport	2
D-glucose transmembrane transport	2
transport	2
carbohydrate:monoatomic cation symporter activity	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
glucoside transport	1
intestinal hexose absorption	1
metal ion transport	1
monosaccharide transmembrane transport	1
organic hydroxy compound transport	1
epithelial fluid transport	1
renal absorption	1
hexose import across plasma membrane	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
intestinal absorption	1
vascular transport	1
cellular process	1
galactose transmembrane transport	1
myo-inositol transmembrane transporter activity	1
transmembrane transporter activity	1
D-glucose transmembrane transporter activity	1
monosaccharide transmembrane transporter activity	1
pentose transmembrane transport	1
fucose transmembrane transport	1
alpha-glucoside transport	1
glucoside transmembrane transporter activity	1
galactose 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
endosome	1

Protein interactions and networks

STRING

1774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC5A1	TAS1R3	Q7RTX0	949
SLC5A1	TAS1R2	Q8TE23	949
SLC5A1	EGFR	P00533	938
SLC5A1	GNAT3	A8MTJ3	896
SLC5A1	SLC2A2	P11168	889
SLC5A1	SLC2A1	P11166	865
SLC5A1	SLC2A5	P22732	851
SLC5A1	GCG	P01275	847
SLC5A1	Q92681	Q92681	836
SLC5A1	SLC15A1	P46059	800
SLC5A1	SLC60A2	Q5TF39	791
SLC5A1	INS	P01308	780
SLC5A1	TAS1R1	Q7RTX1	764
SLC5A1	DPP4	P27487	762
SLC5A1	GLP1R	P43220	749

IntAct

7 interactions, top by confidence:

A	B	Type	Score
SLC5A1	EGFR	psi-mi:“MI:0915”(physical association)	0.520
SLC5A1	CD63	psi-mi:“MI:0914”(association)	0.350
SLC5A1	SLC5A10	psi-mi:“MI:0914”(association)	0.350
AXL	ILVBL	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (12): SLC5A1 (Affinity Capture-Western), PAWR (Affinity Capture-Western), SLC5A1 (Synthetic Lethality), HSPA1A (Affinity Capture-Western), SLC5A1 (Affinity Capture-RNA), MUC5AC (Affinity Capture-MS), CD63 (Affinity Capture-MS), SLC5A1 (Proximity Label-MS), CCDC137 (Affinity Capture-MS), CHD3 (Affinity Capture-MS), SLC5A10 (Affinity Capture-MS), KIAA0196 (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

1 interactions.

A	Effect	B	Mechanism
PER1	“down-regulates quantity by repression”	SLC5A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	23
Uncertain significance	231
Likely benign	199
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1407543	NM_000343.4(SLC5A1):c.875G>A (p.Cys292Tyr)	Pathogenic
1425355	NM_000343.4(SLC5A1):c.1394_1395insT (p.Pro466fs)	Pathogenic
1686213	NM_000343.4(SLC5A1):c.1496G>C (p.Arg499Pro)	Pathogenic
2016672	NM_000343.4(SLC5A1):c.824del (p.Pro275fs)	Pathogenic
2103820	NM_000343.4(SLC5A1):c.1388T>A (p.Leu463Ter)	Pathogenic
2431781	NM_000343.4(SLC5A1):c.1666-2del	Pathogenic
2812666	NM_000343.4(SLC5A1):c.673G>T (p.Glu225Ter)	Pathogenic
2820703	NM_000343.4(SLC5A1):c.1683G>A (p.Trp561Ter)	Pathogenic
341251	NM_000343.4(SLC5A1):c.1230C>G (p.Tyr410Ter)	Pathogenic
3587897	NM_000343.4(SLC5A1):c.866G>A (p.Trp289Ter)	Pathogenic
3661475	NM_000343.4(SLC5A1):c.1151C>G (p.Ser384Ter)	Pathogenic
3729850	NM_000343.4(SLC5A1):c.259del (p.Leu87fs)	Pathogenic
4725887	NM_000343.4(SLC5A1):c.1065C>A (p.Cys355Ter)	Pathogenic
4730057	NM_000343.4(SLC5A1):c.1566del (p.Cys522fs)	Pathogenic
4734011	NM_000343.4(SLC5A1):c.1613_1614insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCCATTTCTTT (p.Phe538_Ile539insPhePhePhePhePhePheXaaXaaXaaXaaSerArgSerProAspLeuValIleArgProProArgProProLysValLeuGlyLeuGlnAlaTer)	Pathogenic
529229	NM_000343.4(SLC5A1):c.1370A>G (p.Gln457Arg)	Pathogenic
803681	NM_000343.4(SLC5A1):c.799C>T (p.Arg267Ter)	Pathogenic
803683	NM_000343.4(SLC5A1):c.1695del (p.Asn565fs)	Pathogenic
973540	NM_000343.4(SLC5A1):c.187C>T (p.Arg63Ter)	Pathogenic
992967	NM_000343.4(SLC5A1):c.765C>G (p.Cys255Trp)	Pathogenic
12907	NM_000343.4(SLC5A1):c.82G>A (p.Asp28Asn)	Likely pathogenic
1325095	NM_000343.4(SLC5A1):c.226del (p.Ala76fs)	Likely pathogenic
1514148	NM_000343.4(SLC5A1):c.372+1_372+2insCTTATAT	Likely pathogenic
1522161	NM_000343.4(SLC5A1):c.1021+1G>A	Likely pathogenic
2138439	NM_000343.4(SLC5A1):c.1496G>A (p.Arg499His)	Likely pathogenic
2631995	NM_000343.4(SLC5A1):c.475T>C (p.Ser159Pro)	Likely pathogenic
2633069	NM_000343.4(SLC5A1):c.1577dup (p.Tyr526Ter)	Likely pathogenic
2633895	NM_000343.4(SLC5A1):c.200G>A (p.Trp67Ter)	Likely pathogenic
2800411	NM_000343.4(SLC5A1):c.665-2A>G	Likely pathogenic
3255338	NM_000343.4(SLC5A1):c.947T>C (p.Leu316Pro)	Likely pathogenic

SpliceAI

2287 predictions. Top by Δscore:

Variant	Effect	Δscore
22:32043413:GTGG:G	donor_gain	1.0000
22:32043415:GG:G	donor_gain	1.0000
22:32043416:GG:G	donor_gain	1.0000
22:32043417:G:GG	donor_gain	1.0000
22:32067035:GGAAT:G	donor_gain	1.0000
22:32067036:GAAT:G	donor_gain	1.0000
22:32067036:GAATG:G	donor_gain	1.0000
22:32067040:G:GG	donor_gain	1.0000
22:32067960:A:AG	acceptor_gain	1.0000
22:32067961:TTTCA:T	acceptor_loss	1.0000
22:32067962:TTCAG:T	acceptor_loss	1.0000
22:32067963:TCAGG:T	acceptor_loss	1.0000
22:32067964:CAG:C	acceptor_loss	1.0000
22:32067965:A:AG	acceptor_gain	1.0000
22:32067965:AGGCC:A	acceptor_loss	1.0000
22:32067966:G:GA	acceptor_gain	1.0000
22:32067966:GGCC:G	acceptor_gain	1.0000
22:32068024:GGG:G	donor_gain	1.0000
22:32068025:GG:G	donor_gain	1.0000
22:32068025:GGG:G	donor_gain	1.0000
22:32068025:GGGT:G	donor_loss	1.0000
22:32068026:GG:G	donor_gain	1.0000
22:32068026:GGT:G	donor_loss	1.0000
22:32068027:G:GG	donor_gain	1.0000
22:32068028:TAAG:T	donor_loss	1.0000
22:32068491:TGCA:T	acceptor_loss	1.0000
22:32068492:GCAG:G	acceptor_loss	1.0000
22:32068493:CAGG:C	acceptor_loss	1.0000
22:32068495:G:GC	acceptor_loss	1.0000
22:32084437:A:AG	acceptor_gain	1.0000

AlphaMissense

4342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:32099211:A:C	S437R	1.000
22:32099213:C:A	S437R	1.000
22:32099213:C:G	S437R	1.000
22:32043408:G:A	G43R	0.999
22:32043408:G:C	G43R	0.999
22:32043409:G:A	G43E	0.999
22:32049979:T:C	F58L	0.999
22:32049981:C:A	F58L	0.999
22:32049981:C:G	F58L	0.999
22:32049982:T:C	F59L	0.999
22:32049984:C:A	F59L	0.999
22:32049984:C:G	F59L	0.999
22:32066939:G:A	G71E	0.999
22:32066956:A:C	S77R	0.999
22:32066958:T:A	S77R	0.999
22:32066958:T:G	S77R	0.999
22:32066968:A:C	S81R	0.999
22:32066970:T:A	S81R	0.999
22:32066970:T:G	S81R	0.999
22:32083074:G:A	G195E	0.999
22:32084911:G:C	Q299H	0.999
22:32084911:G:T	Q299H	0.999
22:32085017:A:C	S335R	0.999
22:32085019:C:A	S335R	0.999
22:32085019:C:G	S335R	0.999
22:32085021:G:C	R336P	0.999
22:32086279:T:A	C361S	0.999
22:32086279:T:C	C361R	0.999
22:32086280:G:C	C361S	0.999
22:32086281:T:G	C361W	0.999

dbSNP variants (sampled 300 via entrez): RS1000023535 (22:32046594 C>T), RS1000045257 (22:32041956 G>A), RS1000103317 (22:32080261 A>C), RS1000142211 (22:32105196 T>A), RS1000247576 (22:32108508 G>A,C,T), RS1000356979 (22:32055525 C>T), RS1000418495 (22:32087977 A>T), RS1000492108 (22:32082203 G>A,C), RS1000523851 (22:32094362 T>C), RS1000561188 (22:32042268 C>T), RS1000566673 (22:32087205 C>A,T), RS1000575150 (22:32048798 C>A,T), RS1000634664 (22:32062186 A>G), RS1000727725 (22:32080368 T>C), RS1000774252 (22:32067370 T>A)

Disease associations

OMIM: gene MIM:182380 | disease phenotypes: MIM:606824

GenCC curated gene-disease

Disease	Classification	Inheritance
glucose-galactose malabsorption	Definitive	Autosomal recessive

Mondo (1): glucose-galactose malabsorption (MONDO:0011731)

Orphanet (1): Glucose-galactose malabsorption (Orphanet:35710)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000787	Nephrolithiasis
HP:0000790	Hematuria
HP:0001508	Failure to thrive
HP:0001824	Weight loss
HP:0001942	Metabolic acidosis
HP:0001944	Dehydration
HP:0001945	Fever
HP:0001986	Hypertonic dehydration
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002028	Chronic diarrhea
HP:0003072	Hypercalcemia
HP:0003076	Glycosuria
HP:0003228	Hypernatremia
HP:0003270	Abdominal distention
HP:0003623	Neonatal onset
HP:0004395	Malnutrition
HP:0004924	Abnormal oral glucose tolerance
HP:0030143	Hyperactive bowel sounds
HP:0033310	Osmotic diarrhea

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004643_3	1,5-anhydroglucitol levels	6.000000e-13
GCST005165_1	GLP-1 levels in response to oral glucose tolerance test (120 minutes)	4.000000e-08
GCST005166_1	GIP levels in response to oral glucose tolerance test (120 minutes)	3.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008009	1,5 anhydroglucitol measurement
EFO:0004307	glucose tolerance test
EFO:0008465	glucagon-like peptide-1 measurement
EFO:0008464	glucose-dependent insulinotropic peptide measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562602	Glucose-Galactose Malabsorption (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4979 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,283 (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
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
CHEMBL4297625	LICOGLIFLOZIN	2	513
CHEMBL450044	SERGLIFLOZIN ETABONATE	2	1,055
CHEMBL5314923	MIZAGLIFLOZIN	2	115

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

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	7.66	pIC50
mizagliflozin	Inhibition	7.57	pKi
sotagliflozin	Inhibition	7.44	pIC50
dapagliflozin	Inhibition	6.4	pIC50
enavogliflozin	Inhibition	6.26	pIC50
canagliflozin	Inhibition	6.2	pIC50
ipragliflozin	Inhibition	5.73	pIC50
ertugliflozin	Inhibition	5.71	pIC50
remogliflozin	Inhibition	5.3	pKi
bexagliflozin	Inhibition	5.25	pIC50
sergliflozin	Inhibition	5.1	pKi
empagliflozin	Inhibition	5.1	pIC50
tofogliflozin	Inhibition	5.07	pIC50

Binding affinities (BindingDB)

726 measured of 832 human assays (832 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(2-dimethylaminoethyl)-1-[4-[4-[[5-[(2S, 3R, 4S, 5S, 6R)-6-ethyl-3,4,5-trihydroxy-tetrahydropyran-2-yl]-2-methyl-phenyl] methyl] phenyl] butyrylamino] cyclohexyl formamide	IC50	0.22 nM	US-12324812: Glucopyranosyl derivatives and their uses
N-(2-dimethylaminoethyl)-1-[4-[4-[[2-methyl-5-[(2S, 3R, 4S, 5S, 6R)-3,4,5-trihydroxy-6-propyl-tetrahydropyran-2-yl] phenyl] methyl]phenyl] butyrylamino] cyclohexylformamide	IC50	0.25 nM	US-12324812: Glucopyranosyl derivatives and their uses
(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-[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-[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
(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-[(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-[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-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
(3R,4R)-N-[5-(3-tert-butylphenyl)-1-(2-chlorophenyl)pyrazol-3-yl]-4-methyl-5-oxopyrrolidine-3-carboxamide	IC50	0.7 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(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-[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
(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-[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-[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
(3R)-N-[5-(3-tert-butylphenyl)-1-(2-chlorophenyl)pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	0.9 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-methoxyphenyl)methyl]-2,3-dihydro-1-benzothiophen-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.902 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[5-chloro-6-[(4-ethylphenyl)methyl]-2,3-dihydro-1,4-benzodioxin-8-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.923 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-benzothiophen-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	0.976 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(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	IC50	0.978 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[4-chloro-5-[(4-cyclopropylphenyl)methyl]-2,3-dihydro-1-benzofuran-7-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	1.09 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(3R)-N-[1-(2-chlorophenyl)-5-[3-(1,1-difluoropropyl)phenyl]pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.1 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R,4R)-N-[5-[3-(1,1-difluoropropyl)phenyl]-1-phenylpyrazol-3-yl]-4-methyl-5-oxopyrrolidine-3-carboxamide	IC50	1.1 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3S)-N-[1-(5-ethoxy-2-fluorophenyl)-5-[3-[[(2R)-1,1,1-trifluoropropan-2-yl]oxymethyl]phenyl]pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.1 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(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	IC50	1.15 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
(2S,3R,4R,5S,6R)-2-[7-chloro-6-[(4-methoxyphenyl)methyl]-1,3-benzodioxol-4-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	1.15 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors
N-(2-dimethylaminoethyl)-1-[4-[4-[[2-methyl-5-[(1S, 2S, 3S, 4R, 5S)-2,3,4,-trihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo [3.2.1] octane-5-yl] phenyl] methyl] phenyl] butyrylamino] cyclohexyl formamide	IC50	1.18 nM	US-12324812: Glucopyranosyl derivatives and their uses
(3R)-N-[5-(3-tert-butylphenyl)-1-(3-chlorophenyl)pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.2 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R)-N-[1-(2-chlorophenyl)-5-[3-(trifluoromethoxy)phenyl]pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.3 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R)-N-[5-[3-(1,1-difluoropropyl)phenyl]-1-(2-methylphenyl)pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.3 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R,4R)-N-[1-(2-chlorophenyl)-5-[3-(trifluoromethoxy)phenyl]pyrazol-3-yl]-4-methyl-5-oxopyrrolidine-3-carboxamide	IC50	1.3 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R,4R)-N-[1-(2-chlorophenyl)-5-[3-(1,1-difluoropropyl)phenyl]pyrazol-3-yl]-4-methyl-5-oxopyrrolidine-3-carboxamide	IC50	1.3 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R)-N-[1-(2-fluorophenyl)-5-(3-propylphenyl)pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.4 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R)-N-[5-(3-tert-butylphenyl)-1-(3-methylphenyl)pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.4 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R,4R)-N-[1-(2-chlorophenyl)-5-[3-(trifluoromethyl)phenyl]pyrazol-3-yl]-4-methyl-5-oxopyrrolidine-3-carboxamide	IC50	1.4 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3R,4R)-N-[1-(2-chlorophenyl)-5-[3-(2,2,2-trifluoroethoxy)phenyl]pyrazol-3-yl]-4-methyl-5-oxopyrrolidine-3-carboxamide	IC50	1.4 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3S)-N-[1-(2-fluoro-5-propan-2-yloxyphenyl)-5-[3-(2,2,2-trifluoroethoxymethyl)phenyl]pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.4 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(3S)-N-[1-(2-fluoro-5-propan-2-yloxyphenyl)-5-[3-[[(2R)-1,1,1-trifluoropropan-2-yl]oxymethyl]phenyl]pyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.4 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(1S,2S,3S,4R,5S)-5-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-ethylphenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol	IC50	1.49 nM	US-10011627: C-aryl glucoside derivative, preparation methods thereof, and medical applications thereof
(3R)-N-[5-[3-(1,1-difluoro-2-methylpropyl)phenyl]-1-phenylpyrazol-3-yl]-5-oxopyrrolidine-3-carboxamide	IC50	1.5 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
1,1-dioxo-N-[1-phenyl-5-(3-propylphenyl)pyrazol-3-yl]thiane-4-carboxamide	IC50	1.5 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
4-oxo-N-[1-phenyl-5-(3-propylphenyl)pyrazol-3-yl]-5-azaspiro[2.4]heptane-7-carboxamide	IC50	1.5 nM	US-8846746: Pyrazole compound and pharmaceutical use thereof
(2S,3R,4R,5S,6R)-2-[5-chloro-6-[(4-ethoxyphenyl)methyl]-3,4-dihydro-2H-chromen-8-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	IC50	1.55 nM	US-9034921: Diphenylmethane derivatives as SGLT2 inhibitors

ChEMBL bioactivities

1909 potent at pChembl≥5 of 2045 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	IC50	0.16	nM	CHEMBL485830
9.77	IC50	0.17	nM	CHEMBL521026
9.30	IC50	0.5	nM	LICOGLIFLOZIN
9.24	IC50	0.58	nM	CHEMBL5835461
9.15	IC50	0.7	nM	CHEMBL3690855
9.05	IC50	0.9	nM	CHEMBL3686477
9.01	IC50	0.98	nM	CHEMBL5873761
8.96	IC50	1.1	nM	CHEMBL3686485
8.96	IC50	1.1	nM	CHEMBL3690821
8.96	IC50	1.1	nM	CHEMBL3695107
8.96	IC50	1.1	nM	CHEMBL4073540
8.92	IC50	1.2	nM	CHEMBL3686471
8.92	IC50	1.2	nM	CHEMBL5887409
8.92	IC50	1.2	nM	CHEMBL5959697
8.92	IC50	1.2	nM	CHEMBL6059327
8.89	IC50	1.3	nM	CHEMBL3686475
8.89	IC50	1.3	nM	CHEMBL3686489
8.89	IC50	1.3	nM	CHEMBL3690854
8.89	IC50	1.3	nM	CHEMBL3690868
8.89	IC50	1.3	nM	CHEMBL5933905
8.85	IC50	1.4	nM	CHEMBL3686463
8.85	IC50	1.4	nM	CHEMBL3686472
8.85	IC50	1.4	nM	CHEMBL3690863
8.85	IC50	1.4	nM	CHEMBL3690875
8.85	IC50	1.4	nM	CHEMBL3695105
8.85	IC50	1.4	nM	CHEMBL3695108
8.83	IC50	1.49	nM	CHEMBL6044817
8.82	IC50	1.5	nM	CHEMBL3686483
8.82	IC50	1.5	nM	CHEMBL3690942
8.82	IC50	1.5	nM	CHEMBL3690989
8.80	IC50	1.6	nM	CHEMBL3686422
8.80	IC50	1.6	nM	CHEMBL4084883
8.77	IC50	1.7	nM	CHEMBL3686428
8.77	IC50	1.7	nM	CHEMBL3686484
8.77	IC50	1.7	nM	CHEMBL3695096
8.77	IC50	1.7	nM	CHEMBL3695097
8.77	IC50	1.7	nM	CHEMBL3695109
8.77	IC50	1.7	nM	CHEMBL4102834
8.74	IC50	1.8	nM	CHEMBL3686379
8.74	IC50	1.8	nM	CHEMBL3686440
8.74	IC50	1.8	nM	CHEMBL3695170
8.74	IC50	1.8	nM	CHEMBL4069350
8.74	IC50	1.82	nM	CHEMBL5864663
8.72	IC50	1.9	nM	CHEMBL3686447
8.72	IC50	1.9	nM	CHEMBL5913269
8.72	IC50	1.9	nM	CHEMBL6027169
8.70	IC50	2	nM	CHEMBL3686429
8.70	IC50	2	nM	CHEMBL3695098
8.70	IC50	2	nM	CHEMBL4093607
8.70	IC50	2	nM	CHEMBL486028

PubChem BioAssay actives

521 with measured affinity, of 901 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)-1-[(2S)-2-[[(2S)-2,5-diamino-5-oxopentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carboxylic acid	386046: Inhibition of human SGLT1 expressed in xenopus laevis oocyte assessed as inhibition of methyl-alpha-D-[14C]glucopyranoside uptake after 1 hrs	ic50	0.0002	uM
(2S)-2-[[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-amino-5-oxopentanoic acid	386046: Inhibition of human SGLT1 expressed in xenopus laevis oocyte assessed as inhibition of methyl-alpha-D-[14C]glucopyranoside uptake after 1 hrs	ic50	0.0002	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	1721967: Inhibition of SGLT1 (unknown origin)	ic50	0.0005	uM
N-[1-(4-methylpiperazine-1-carbonyl)cyclopropyl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0011	uM
N-[2-methyl-1-(4-methylpiperidin-1-yl)-1-oxopropan-2-yl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0016	uM
N-[2-(dimethylamino)ethyl]-N,2-dimethyl-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0017	uM
N-[2-methyl-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0018	uM
(2R)-2-[[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoic acid	386046: Inhibition of human SGLT1 expressed in xenopus laevis oocyte assessed as inhibition of methyl-alpha-D-[14C]glucopyranoside uptake after 1 hrs	ic50	0.0020	uM
(2S,3R,4R,5S,6R)-2-[3-[[4-[3-[[3-(dimethylamino)-2,2-dimethylpropyl]amino]propoxy]phenyl]methyl]-4-methylphenyl]-6-methylsulfanyloxane-3,4,5-triol	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0020	uM
(2S)-1-[(2R)-2-[[(2S)-2,5-diamino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid	386046: Inhibition of human SGLT1 expressed in xenopus laevis oocyte assessed as inhibition of methyl-alpha-D-[14C]glucopyranoside uptake after 1 hrs	ic50	0.0021	uM
N-[2-(dimethylamino)ethyl]-2-methyl-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0022	uM
2,2-dimethyl-3-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butylamino]propanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0023	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	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0024	uM
2-methyl-N-(1-methylpiperidin-4-yl)-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0027	uM
N-[2-methyl-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenoxy]butanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0029	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-cyclopropyl-2-hydroxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390386: Inhibition of human small intestinal SGLT1 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	0.0030	uM
(2S,3R,4R,5S,6R)-2-[5-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-ethyl-2-hydroxyphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390386: Inhibition of human small intestinal SGLT1 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	0.0030	uM
(2S,3R,4R,5S,6R)-2-[3-[[4-[3-[(1-hydroxy-2-methylpropan-2-yl)amino]propoxy]phenyl]methyl]-4-methylphenyl]-6-methylsulfanyloxane-3,4,5-triol	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0033	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	1390386: Inhibition of human small intestinal SGLT1 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	0.0040	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	1390386: Inhibition of human small intestinal SGLT1 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	0.0050	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	1390386: Inhibition of human small intestinal SGLT1 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	0.0050	uM
N-[2,2-dimethyl-3-(4-methylpiperazin-1-yl)-3-oxopropyl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0068	uM
N-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0084	uM
N-[2-methyl-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-4-[4-[[5-propan-2-yl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1H-pyrazol-4-yl]methyl]phenyl]butanamide	725908: Inhibition of human SGLT1 expressed in COS7 cells assessed as inhibition [14C]-AMG cellular uptake	ic50	0.0100	uM
N-(2-methyl-1-oxo-1-piperazin-1-ylpropan-2-yl)-4-[3-methyl-4-[[5-propan-2-yl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1H-pyrazol-4-yl]methyl]phenyl]butanamide	725908: Inhibition of human SGLT1 expressed in COS7 cells assessed as inhibition [14C]-AMG cellular uptake	ic50	0.0110	uM
N-(1-hydroxy-2-methylpropan-2-yl)-4-[4-[[5-propan-2-yl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1H-pyrazol-4-yl]methyl]phenyl]butanamide	725908: Inhibition of human SGLT1 expressed in COS7 cells assessed as inhibition [14C]-AMG cellular uptake	ic50	0.0120	uM
(2S,3R,4R,5S,6R)-2-[7-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-5-fluoro-6-(hydroxymethyl)oxane-3,4-diol	1422283: Inhibition of human small intestinal SGLT1 expressed in CHOK1 cells assessed as reduction in Na-dependent [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition measured after 2 hrs by TopCount method	ic50	0.0140	uM
2-methyl-1-(4-methylpiperazin-1-yl)-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butylamino]propan-1-one	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0148	uM
N-(2-methyl-1-oxo-1-piperazin-1-ylpropan-2-yl)-4-[4-[[5-propan-2-yl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1H-pyrazol-4-yl]methyl]phenyl]butanamide	725908: Inhibition of human SGLT1 expressed in COS7 cells assessed as inhibition [14C]-AMG cellular uptake	ic50	0.0150	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	1888490: Inhibition of human SGLT1 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0152	uM
(2S,3R,4R,5S,6R)-2-[3-[[4-(2,3-dihydroxypropoxy)phenyl]methyl]-4-methylphenyl]-6-methylsulfanyloxane-3,4,5-triol	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0154	uM
(2R,3S,4S,5R,6S)-2-[4-chloro-3-[(4-methoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol	1874432: Inhibition of full length N-terminal HA-tagged human SGLT1 expressed in HEK293 cells assessed as inhibition of [14C]AMG uptake	ic50	0.0159	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	1888490: Inhibition of human SGLT1 expressed in CHO cells by methyl-alpha-D-glucopyranoside assay	ic50	0.0169	uM
(2S,3R,4R,5S,6R)-2-[3-(3-bicyclo[4.2.0]octa-1(6),2,4-trienylmethyl)-4-ethylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	1390386: Inhibition of human small intestinal SGLT1 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	0.0180	uM
(E)-N-(1-hydroxy-2-methylpropan-2-yl)-4-[4-[[4-hydroxy-2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]phenyl]-2,2-dimethylbut-3-enamide	1515418: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in sodium-dependent glucose uptake after 30 mins in presence of [14C]-methyl-alpha -D-glucopyranoside by microbeta counting method	ic50	0.0210	uM
(E)-N-(1,3-dihydroxy-2-methylpropan-2-yl)-4-[4-[[4-hydroxy-2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)thian-2-yl]phenyl]methyl]phenyl]but-3-enamide	1422627: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in Na-dependent [14C]-methyl-alpha-D-glucopyranoside uptake after 30 mins by microbeta counting method	ic50	0.0220	uM
(E)-4-[4-[[2,4-dimethyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]phenyl]-N-(1-hydroxy-2-methylpropan-2-yl)-2,2-dimethylbut-3-enamide	1515418: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in sodium-dependent glucose uptake after 30 mins in presence of [14C]-methyl-alpha -D-glucopyranoside by microbeta counting method	ic50	0.0220	uM
(2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-methylindol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1064965: Inhibition of human SGLT1-mediated [14C]-AMG uptake expressed in CHOK cells preincubated for 10 mins followed by [14C]-AMG addition measured after 120 mins by liquid scintillation counting analysis	ic50	0.0220	uM
(E)-N-(1-hydroxy-2-methylpropan-2-yl)-4-[4-[[4-hydroxy-2-propan-2-yl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]phenyl]-2,2-dimethylbut-3-enamide	1515418: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in sodium-dependent glucose uptake after 30 mins in presence of [14C]-methyl-alpha -D-glucopyranoside by microbeta counting method	ic50	0.0230	uM
N-[2-(dimethylamino)ethyl]-2-methyl-2-[4-[4-[[5-propan-2-yl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1H-pyrazol-4-yl]methyl]phenyl]butanoylamino]propanamide	725908: Inhibition of human SGLT1 expressed in COS7 cells assessed as inhibition [14C]-AMG cellular uptake	ic50	0.0230	uM
(2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-[2-hydroxy-4-methyl-5-[(4-methylphenyl)methyl]phenyl]thiane-3,4,5-triol	1422627: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in Na-dependent [14C]-methyl-alpha-D-glucopyranoside uptake after 30 mins by microbeta counting method	ic50	0.0250	uM
N-(2-methyl-1-oxo-1-piperidin-1-ylpropan-2-yl)-4-[4-[[5-propan-2-yl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1H-pyrazol-4-yl]methyl]phenyl]butanamide	725908: Inhibition of human SGLT1 expressed in COS7 cells assessed as inhibition [14C]-AMG cellular uptake	ic50	0.0250	uM
2-methyl-2-[[2-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenoxy]acetyl]amino]propanamide	1436422: Inhibition of human HA-tagged SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake measured after 1 to 2 hrs by scintillation counting method	ic50	0.0253	uM
(2R,3R,4S,5S,6R)-2-[4-chloro-3-[(4-cyclopropylphenyl)methyl]indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1292293: Inhibition of human SGLT1 expressed in CHO-K1 cells assessed as reduction in [14C]AMG uptake after 120 mins by scintillation counting method	ec50	0.0270	uM
(E)-N-[1-[(2-amino-2-methylpropyl)amino]-2-methyl-1-oxopropan-2-yl]-4-[4-[[4-hydroxy-2-propan-2-yl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]-3-methylphenyl]-2,2-dimethylbut-3-enamide	1515418: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in sodium-dependent glucose uptake after 30 mins in presence of [14C]-methyl-alpha -D-glucopyranoside by microbeta counting method	ic50	0.0270	uM
1-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-3-[2-[4-[[4-hydroxy-2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]phenyl]ethyl]urea	1422627: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in Na-dependent [14C]-methyl-alpha-D-glucopyranoside uptake after 30 mins by microbeta counting method	ic50	0.0280	uM
(E)-N-[1-[2-(dimethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]-4-[4-[[4-methoxy-2-propan-2-yl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]phenyl]-2,2-dimethylbut-3-enamide	1515418: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in sodium-dependent glucose uptake after 30 mins in presence of [14C]-methyl-alpha -D-glucopyranoside by microbeta counting method	ic50	0.0290	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149430: Binding affinity to human SLC5A1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0299	uM
(E)-4-[4-[[4-hydroxy-2-propan-2-yl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]-3-methylphenyl]-2,2-dimethyl-N-(2-methyl-1-oxo-1-piperazin-1-ylpropan-2-yl)but-3-enamide	1515418: Inhibition of human SGLT1 expressed in CHOK1 cells assessed as reduction in sodium-dependent glucose uptake after 30 mins in presence of [14C]-methyl-alpha -D-glucopyranoside by microbeta counting method	ic50	0.0300	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	1390386: Inhibition of human small intestinal SGLT1 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	0.0320	uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylglucoside	decreases reaction, increases uptake, affects cotreatment, affects binding	4
Glucose	affects cotreatment, decreases reaction, increases uptake, affects transport, affects uptake	3
Phlorhizin	affects cotreatment, affects binding, decreases reaction, increases uptake	3
sodium arsenite	affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	2
Doxorubicin	decreases expression	2
Galactose	affects cotreatment, decreases reaction, increases uptake, affects transport	2
sotorasib	affects cotreatment, decreases expression	1
urushiol	increases expression	1
methyleugenol	decreases expression	1
naringenin	decreases reaction, increases uptake	1
sodium arsenate	decreases expression, increases abundance	1
isoquercitrin	decreases reaction, increases uptake	1
hyperoside	increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
hydroquinone	increases expression	1
caffeic acid	increases expression	1
arsenic pentoxide	decreases expression	1
polydatin	affects uptake	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
spiraeoside	increases uptake, decreases reaction	1
luteolin 4’-O-glucoside	increases uptake, decreases reaction	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
abrine	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects uptake	1
Sunitinib	decreases expression	1
Air Pollutants	increases expression	1

ChEMBL screening assays

132 unique, capped per target: 124 binding, 6 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1040744	Binding	Inhibition of human SGLT1 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methylglucopyranoside uptake	Novel L-xylose derivatives as selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. — J Med Chem
CHEMBL4004099	ADMET	Inhibition of human SGLT1 expressed in HEK293 cells assessed as reduction in 2-deoxyglucose uptake pretreated for 10 mins followed by 2-deoxyglucose addition in presence of sodium buffer measured after 1 hr by resazurin dye based fluorescen	Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation. — J Med Chem
CHEMBL5723536	Functional	Affinity On-target Cellular interaction: (Inhibition of radiolabelled [14C]AMG uptake by COS-7 cells expressing SLC5A1) EUB0002638a SLC5A1	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1QK	Abcam K-562 SLC5A1 KO	Cancer cell line	Female
CVCL_D2M6	Abcam Raji SLC5A1 KO	Cancer cell line	Male
CVCL_D4W5	LS180-SLC5A1-KO-c4	Cancer cell line	Female
CVCL_D4W6	LS180-SLC5A1-KO-c5	Cancer cell line	Female
CVCL_WQ55	Abcam Jurkat SLC5A1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04109352	Not specified	UNKNOWN	Labelled Carbon Sucrose Breath Test (13C-SBT) as a Marker of Environmental Enteropathy
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening