Sotagliflozin

Summary

Sotagliflozin (CHEMBL3039507) is an approved small-molecule sodium-glucose transport protein subtype 2 inhibitor (ATC A10BK06) targeting SLC5A1 and SLC5A2; indicated across 10 conditions including diabetes mellitus and heart failure.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BK06
• Targets: 2 (SLC5A1, SLC5A2)
• Indications: 10 conditions
• Clinical trials: 58
• Chemistry: 424.9 Da · C21H25ClO5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3039507
Name	Sotagliflozin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	24831714
ChEBI	CHEBI:229226
ATC	A10BK06
Molecular formula	C21H25ClO5S
Molecular weight	424.9
InChIKey	QKDRXGFQVGOQKS-CRSSMBPESA-N

SMILES: CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)SC)O)O)O)Cl

IUPAC name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol

ChEBI definition: An S-glycosyl compound that is 1-thio-β-L-xylopyranose in which the anomeric hydroxy group is replaced by a 4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl group and the thiol is replaced by a methylsulfanediyl group. It is an inhibitor of SGLT1 and SGLT2 that is approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk.

Pharmacological roles (ChEBI): sodium-glucose transport protein subtype 2 inhibitor, hypoglycemic agent, antihypertensive agent, cardioprotective agent, sodium-glucose transport protein subtype 1 inhibitor.

Also known as: Inpefa, LP-802034, LX-4211, LX4211, Sar-439954, Sar439954, Sotagliflozin, Sotagliflozina, Sotagliflozine, Zynquista, SOTAGLIFLOZIN

Patent coverage: 595 distinct patent families (1,661 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,532 (92%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC5A1	Sodium/glucose cotransporter 1	Inhibition	7.44	0%	P13866
SLC5A2	Sodium/glucose cotransporter 2	Inhibition	8.74	0.2%	P31639

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Sodium/glucose cotransporter 2, Sodium/glucose cotransporter 1.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 12 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC5A2	8.82	IC50	1.5	nM	CHEMBL_ACT_18072028
SLC5A2	8.82	IC50	1.5	nM	CHEMBL_ACT_18072074
SLC5A2	8.82	IC50	1.5	nM	CHEMBL_ACT_19001170
SLC5A2	8.74	IC50	1.8	nM	CHEMBL_ACT_18008438
SLC5A2	8.74	IC50	1.8	nM	CHEMBL_ACT_18728727
SLC5A2	8.74	IC50	1.8	nM	CHEMBL_ACT_22883660
SLC5A1	7.46	IC50	34.6	nM	CHEMBL_ACT_18072036
SLC5A1	7.46	IC50	34.6	nM	CHEMBL_ACT_18072075
SLC5A1	7.46	IC50	34.6	nM	CHEMBL_ACT_19001161
SLC5A1	7.44	IC50	36.2	nM	CHEMBL_ACT_18008415
SLC5A1	7.44	IC50	36	nM	CHEMBL_ACT_18728722
SLC5A1	7.44	IC50	36	nM	CHEMBL_ACT_22883657

Target pathways

Aggregated over 2 target gene(s): SLC5A1, SLC5A2.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Disease	2	SLC5A1, SLC5A2
Cellular hexose transport	2	SLC5A1, SLC5A2
Transport of small molecules	2	SLC5A1, SLC5A2
SLC-mediated transmembrane transport	2	SLC5A1, SLC5A2
SLC transporter disorders	2	SLC5A1, SLC5A2
Disorders of transmembrane transporters	2	SLC5A1, SLC5A2
Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM)	1	SLC5A1
Defective SLC5A2 causes renal glucosuria (GLYS1)	1	SLC5A2
Intestinal absorption	1	SLC5A1
Digestion and absorption	1	SLC5A1
Intestinal hexose absorption	1	SLC5A1

Dominant GO biological processes

GO term	Targets
alpha-glucoside transport	2
sodium ion transport	2
renal D-glucose absorption	2
D-glucose import across plasma membrane	2
sodium ion import across plasma membrane	2
D-glucose transmembrane transport	2
monoatomic ion transport	2
transmembrane transport	2
intestinal D-glucose absorption	1
pentose transmembrane transport	1
fucose transmembrane transport	1
galactose transmembrane transport	1
myo-inositol transport	1
transepithelial water transport	1
intestinal hexose absorption	1

Indications & clinical

Indications

10 indications (6 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
diabetes mellitus	4	MONDO:0005015	EFO:0000400
heart failure	4	MONDO:0005252	EFO:0003144
type 1 diabetes mellitus	4	MONDO:0005147	MONDO:0005147
type 2 diabetes mellitus	4	MONDO:0005148	MONDO:0005148
chronic kidney disease	4	MONDO:0005300	EFO:0003884
nasopharyngeal neoplasm	4	MONDO:0005375	EFO:0004252
hypertrophic cardiomyopathy	3	MONDO:0005045	EFO:0000538
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086
cardiomyopathy	0	MONDO:0004994	EFO:0000318

Clinical trials

Total trials: 58.

Phase distribution

Phase	Trials
PHASE1	22
PHASE3	19
PHASE2	11
PHASE4	3
PHASE1/PHASE2	1
EARLY_PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07547878	PHASE4	NOT_YET_RECRUITING	Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)
NCT05562063	PHASE4	COMPLETED	Sotagliflozin in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients
NCT06618976	PHASE4	COMPLETED	Antithrombotic Activities of Sotagliflozin vs. Empagliflozin
NCT06082063	PHASE3	RECRUITING	Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes
NCT06217302	PHASE3	RECRUITING	Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease
NCT06481891	PHASE3	RECRUITING	A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy
NCT02384941	PHASE3	COMPLETED	Efficacy, Safety, and Tolerability Study of Sotagliflozin as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy
NCT02421510	PHASE3	COMPLETED	Efficacy, Safety, and Tolerability Study of Sotagliflozin as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy
NCT02531035	PHASE3	COMPLETED	A Phase 3 Study to Evaluate the Safety of Sotagliflozin in Patients With Type 1 Diabetes Who Have Inadequate Glycemic Control With Insulin Therapy Alone
NCT02926937	PHASE3	COMPLETED	Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus Not Currently Treated With Antidiabetic Therapy
NCT02926950	PHASE3	COMPLETED	Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin
NCT03066830	PHASE3	COMPLETED	Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin
NCT03242018	PHASE3	COMPLETED	A Study to Evaluate Safety and Effects of Sotagliflozin 400 and 200 mg on Glucose Control in Participants With Type 2 Diabetes, Severe Impairment of Kidney Function and Inadequate Blood Sugar Control
NCT03242252	PHASE3	COMPLETED	Safety and Efficacy Study of Sotagliflozin on Glucose Control in Participants With Type 2 Diabetes, Moderate Impairment of Kidney Function, and Inadequate Blood Sugar Control
NCT03285594	PHASE3	COMPLETED	Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents
NCT03315143	PHASE3	TERMINATED	Effect of Sotagliflozin on Cardiovascular and Renal Events in Participants With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk
NCT03332771	PHASE3	COMPLETED	Efficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Participants With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy
NCT03351478	PHASE3	COMPLETED	Efficacy and Safety of Sotagliflozin Versus Placebo and Empagliflozin in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking a DPP4 Inhibitor Alone or With Metformin
NCT03386344	PHASE3	TERMINATED	Efficacy and Bone Safety of Sotagliflozin 400 and 200 mg Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
NCT03521934	PHASE3	TERMINATED	Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF Trial)
NCT03760965	PHASE3	TERMINATED	Efficacy and Safety of Sotagliflozin Versus Placebo in Chinese Patients With Type 2 Diabetes Mellitus Not Adequately Controlled by Diet and Exercise
NCT03761134	PHASE3	TERMINATED	Efficacy and Safety of Sotagliflozin Versus Placebo in Chinese Patients With Type 2 Diabetes Mellitus Not Adequately Controlled by Metformin With or Without Sulfonylurea
NCT05696366	PHASE1/PHASE2	RECRUITING	Combination Adjunctive Therapy to Address Multiple Metabolic Imbalances in Type 1 Diabetes
NCT06147232	PHASE2	NOT_YET_RECRUITING	Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia
NCT06435156	PHASE2	RECRUITING	Sotagliflozin in Patients With Heart Failure Symptoms and Type 1 Diabetes
NCT07325201	PHASE2	NOT_YET_RECRUITING	Reducing Risk of Diabetic Ketoacidosis in Type 1 Diabetes and Kidney Disease Using Continuous Ketone Monitoring
NCT07572175	PHASE2	NOT_YET_RECRUITING	Sotagliflozin as Prevention of Anthracycline-Related Cardiotoxicity
NCT07594145	PHASE2	NOT_YET_RECRUITING	Precision T1D Platform - New Therapies for Cardio-Renal Complications
NCT01376557	PHASE2	COMPLETED	Safety and Efficacy of LX4211 With Metformin in Type 2 Diabetes Patients With Inadequate Glycemic Control on Metformin
NCT01742208	PHASE2	COMPLETED	Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
NCT02383940	PHASE2	COMPLETED	Efficacy and Safety of Sotagliflozin in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C
NCT02459899	PHASE2	COMPLETED	Dose-ranging Study in Patients With Type 1 Diabetes Mellitus
NCT03292653	PHASE2	TERMINATED	Safety, Tolerability and Pharmacodynamic Activity of Sotagliflozin in Hemodynamically Stable Participants With Worsening Heart Failure
NCT03462069	PHASE2	COMPLETED	Comparison of Pharmacodynamic Effects of Sotagliflozin and Empagliflozin in T2DM Patients With Mild to Moderate Hypertension
NCT01188863	PHASE1	COMPLETED	Study of Two Oral Formulations of LX4211 in Patients With Type 2 Diabetes Mellitus
NCT01292993	PHASE1	COMPLETED	A Study to Evaluate the Interaction of LX4211 and Metformin in Healthy Subjects
NCT01441232	PHASE1	COMPLETED	A Study to Evaluate the Pharmacodynamic Effects of Single-Dose Co-Administration of LX4211 With Januvia® in Type 2 Diabetics
NCT01555008	PHASE1	COMPLETED	Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes and Renal Impairment
NCT01913002	PHASE1	COMPLETED	Study to Define the Electrocardiogram Effects of a Single Dose of LX4211 in Healthy Subjects
NCT01916850	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability and Pharmacokinetics Following Multiple Doses of LX4211 in Healthy Subjects

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

16 molecules share ≥1 primary target. Top 16 by shared-target count:

Molecule	Source	Status	Shared targets
BEXAGLIFLOZIN	ChEMBL + PubChem	Phase 4 (approved)	SLC5A1, SLC5A2
Canagliflozin	ChEMBL + PubChem	Phase 4 (approved)	SLC5A1, SLC5A2
EMPAGLIFLOZIN	ChEMBL + PubChem	Phase 4 (approved)	SLC5A1, SLC5A2
ERTUGLIFLOZIN	ChEMBL + PubChem	Phase 4 (approved)	SLC5A1, SLC5A2
DAPAGLIFLOZIN	ChEMBL	Phase 4 (approved)	SLC5A1, SLC5A2
IPRAGLIFLOZIN	ChEMBL	Phase 4 (approved)	SLC5A1, SLC5A2
TOFOGLIFLOZIN	ChEMBL	Phase 4 (approved)	SLC5A1, SLC5A2
ENAVOGLIFLOZIN	ChEMBL	Phase 3	SLC5A1, SLC5A2
HENAGLIFLOZIN	ChEMBL	Phase 3	SLC5A1, SLC5A2
LICOGLIFLOZIN	ChEMBL	Phase 2	SLC5A1, SLC5A2
LUSEOGLIFLOZIN	ChEMBL	Phase 2	SLC5A1, SLC5A2
REMOGLIFLOZIN ETABONATE	ChEMBL	Phase 2	SLC5A1, SLC5A2
SERGLIFLOZIN ETABONATE	ChEMBL	Phase 2	SLC5A1, SLC5A2
MIZAGLIFLOZIN	ChEMBL	Phase 2	SLC5A1
YM-543 FREE ACID	ChEMBL	Phase 2	SLC5A2
Phlorizin	PubChem	Approved	SLC5A1