Ertugliflozin

Summary

Ertugliflozin (CHEMBL1770248) is an approved small molecule (ATC A10BK04) targeting SLC5A1 and SLC5A2; indicated across 4 conditions including diabetes mellitus and type 2 diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BK04
• Targets: 2 (SLC5A1, SLC5A2)
• Indications: 4 conditions
• Clinical trials: 34
• Chemistry: 436.9 Da · C22H25ClO7

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1770248
Name	Ertugliflozin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	44814423
ATC	A10BK04
Molecular formula	C22H25ClO7
Molecular weight	436.9
InChIKey	MCIACXAZCBVDEE-CUUWFGFTSA-N

SMILES: CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)[C@@]34[C@@H]([C@H]([C@@H]([C@@](O3)(CO4)CO)O)O)O)Cl

IUPAC name: (1S,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol

Also known as: Ertugliflozin, Ertugliflozina, Ertugliflozine, MK-8835, Pf-04971729, PF04971729, CHEMBL1770248, PF-04971729, ERTUGLIFLOZIN, ERTUGLIFLOZINA, ERTUGLIFLOZINE, ertugliflozin

Parent form; salt/anhydrous children: CHEMBL3526992, CHEMBL5315054

Patent coverage: 741 distinct patent families (1,857 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,826 (98%) 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	5.71	0%	P13866
SLC5A2	Sodium/glucose cotransporter 2	Inhibition	9.06	0.2%	P31639

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Sodium/glucose cotransporter 2, Sodium/glucose cotransporter 2, Sodium/glucose cotransporter 1.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
SLC5A2	9.06	IC50	0.87	nM	CHEMBL_ACT_18728728
SLC5A2	9.06	IC50	0.88	nM	CHEMBL_ACT_19001166
SLC5A2	9.06	IC50	0.88	nM	CHEMBL_ACT_25050101
SLC5A2	9.06	IC50	0.88	nM	CHEMBL_ACT_6182842
P53792	8.94	IC50	1.15	nM	CHEMBL_ACT_6183528
SLC5A2	8.62	IC50	2.4	nM	CHEMBL_ACT_18072027
SLC5A1	6.41	IC50	392	nM	CHEMBL_ACT_18072035
SLC5A1	5.71	IC50	1960	nM	CHEMBL_ACT_19001157
SLC5A1	5.71	IC50	1960	nM	CHEMBL_ACT_6182836
SLC5A1	5.7	IC50	2000	nM	CHEMBL_ACT_25050104

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

4 indications (0 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	3	MONDO:0005015	EFO:0000400
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
mitral valve insufficiency	3	MONDO:1030008	HP:0001653
heart failure	2	MONDO:0005252	EFO:0003144

Clinical trials

Total trials: 34.

Phase distribution

Phase	Trials
PHASE3	14
PHASE4	8
PHASE1	7
PHASE2	4
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05644717	PHASE4	RECRUITING	Effect of Erugliflozin On Liver Fat, Liver Fibrosis and Glycemic Control in Type II DM Patients With NASH/NAFLD
NCT06983054	PHASE4	RECRUITING	DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study, a Randomized, Placebo-controlled, Cross-over Study With Ertugliflozin in People With Type 2 Diabetes
NCT07547878	PHASE4	NOT_YET_RECRUITING	Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)
NCT03640221	PHASE4	WITHDRAWN	Ertugliflozin Versus Hydrochlorothiazide in Reducing Sympathetic Neural Overactivity in Patients With Hypertension and Recently-diagnosed Type 2 Diabetes.
NCT04027530	PHASE4	COMPLETED	Renal Oxygenation, Oxygen Consumption and Hemodynamic Kinetics in Type 2 DIabetes: an Ertugliflozin Study.
NCT04071626	PHASE4	TERMINATED	Evaluating Metabolic Mechanisms of Ertugliflozin in Diabetes & Heart Failure
NCT05152940	PHASE4	COMPLETED	ERTU-SODIUM: Study on the Effects of Ertugliflozin on Sodium Storage, Interstitial Volume, and Plasma Volume in HFrEF
NCT05727579	PHASE4	COMPLETED	DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study
NCT01958671	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise (MK-8835-003, VERTIS MONO)
NCT01986855	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)
NCT01986881	PHASE3	COMPLETED	Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)
NCT01999218	PHASE3	COMPLETED	Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)
NCT02033889	PHASE3	COMPLETED	A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).
NCT02036515	PHASE3	COMPLETED	Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)
NCT02099110	PHASE3	COMPLETED	Ertugliflozin and Sitagliptin Co-administration Factorial Study (VERTIS FACTORAL, MK-8835-005)
NCT02226003	PHASE3	COMPLETED	Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017)
NCT02630706	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012)
NCT03717194	PHASE3	COMPLETED	Effect of Ertugliflozin on Cardiac Function in Diabetes
NCT04029480	PHASE3	COMPLETED	Ertugliflozin Type 2 Diabetes Mellitus (T2DM) Pediatric Study (MK-8835/PF-04971729) (MK-8835-059)
NCT04231331	PHASE3	COMPLETED	Ertugliflozin for Functional Mitral Regurgitation
NCT04490681	PHASE3	UNKNOWN	Validation of ERTugliflozin for Inhibiting Cardiac Fibrosis Using Cardiac MRI and Laboratory Parameters in Korean Heart Failure Patients With Nonischemic Cardiomyopathy(VERTICAL)
NCT04600921	PHASE3	TERMINATED	Ertugliflozin to Reduce Arrhythmic Burden in ICD/CRT patientS (ERASe-Trial) - a Phase III Study
NCT04438213	PHASE2	RECRUITING	Ertugliflozin in Chronic Heart Failure
NCT01059825	PHASE2	COMPLETED	Study Of Safety And Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-016)
NCT01096667	PHASE2	COMPLETED	Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042)
NCT03416270	PHASE2	COMPLETED	ERtugliflozin triAl in DIabetes With Preserved or Reduced ejeCtion FrAcTion mEchanistic Evaluation in Heart Failure
NCT00989079	PHASE1	COMPLETED	A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)
NCT01018823	PHASE1	COMPLETED	A Multiple Dose Study Of Ertugliflozin (PF-04971729, MK-8835) In Otherwise Healthy Overweight And Obese Volunteers (MK-8835-037)
NCT01127308	PHASE1	COMPLETED	A Radiolabeled Mass Balance Study of [14C]-Ertugliflozin (PF04971729, MK-8835) In Healthy Male Participants (MK-8835-038)
NCT01223339	PHASE1	COMPLETED	Evaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041)
NCT01948986	PHASE1	COMPLETED	Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Ertugliflozin in Participants With Type 2 Diabetes Mellitus (MK-8835-009)
NCT02115347	PHASE1	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014)
NCT07266779	PHASE1	COMPLETED	Bioequivalence Study of Test Product (T) of Ertugliflozin/Metformin 7.5 mg/ 1000 mg Film Coated Tablets and Reference Product (R) of Segluromet 7.5 mg/ 1000 mg Film Coated Tablets in Healthy, Adult, Human Subjects Under Fed Condition.
NCT04167761	EARLY_PHASE1	COMPLETED	Ertugliflozin: Cardioprotective Effects on Epicardial Fat

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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
SOTAGLIFLOZIN	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