Empagliflozin

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H27ClO7
Molecular Weight	450.909
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@H]1O[C@H]([C@H](O)[C@@H](O)[C@@H]1O)C2=CC=C(Cl)C(CC3=CC=C(O[C@H]4CCOC4)C=C3)=C2

InChI

InChIKey=OBWASQILIWPZMG-QZMOQZSNSA-N

InChI=1S/C23H27ClO7/c24-18-6-3-14(23-22(28)21(27)20(26)19(11-25)31-23)10-15(18)9-13-1-4-16(5-2-13)30-17-7-8-29-12-17/h1-6,10,17,19-23,25-28H,7-9,11-12H2/t17-,19+,20+,21-,22+,23-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204629s000lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=21985634; https://www.boehringer-ingelheim.com/press-release/jardiance-empagliflozin-be-studied-treatment-people-chronic-heart-failure

Empagliflozin is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor designed for the treatment of type 2 diabetes mellitus. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Empagliflozin interacts with diuretics, blood presure medicine and insulin. Jardiance reduces the risk of cardiovascular death in diabetes patients at high cardiovascular risk.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium/glucose cotransporter 2 25 Target ID: CHEMBL3884 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=21985634	Antagonist 2849		3.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 262 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204629s000lbl.pdf	Secondary		Approved 8583	JARDIANCE Approved Use JARDIANCE is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
259 nM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMPAGLIFLOZIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
687 nM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMPAGLIFLOZIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1870 nM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMPAGLIFLOZIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
4740 nM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMPAGLIFLOZIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMPAGLIFLOZIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
13.8% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMPAGLIFLOZIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 P-gp 1741 OAT1 725 OAT3 747 OCT2 779 OATP1B1 1079 OATP1B3 961 MRP2 499 BCRP 910 OATP2B1 157 UGT1A1 246 UGT1A3 89 UGT1A8 37 UGT1A9 148 UGT2B7 197	OAT3 391 OATP1B1 503 OATP1B3 435 OAT1 395 OCT2 434 UGT2B7 456 UGT1A3 470 UGT1A8 323 UGT1A9 423 CYP3A 220	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no [IC50 >1000 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no [IC50 >1000 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT1A3 99	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT1A8 49	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT1A9 155	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT2B7 210	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 114.1 uM]
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 1399 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 295 uM]
OATP2B1 162	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 45.2 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 58.6 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 71.8 uM]

Drug as victim

Target	Modality	Activity
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000PharmR.pdf#page=33 Page: 33.0	yes
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	yes
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	yes
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	yes
UGT1A3 470	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
UGT1A8 323	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
UGT1A9 423	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:82720	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82720
MolPort	MolPort-027-720-828	https://www.molport.com/shop/molecule-link/MolPort-027-720-828
Selleck Chemicals	empagliflozin-bi10773	http://www.selleckchem.com/products/empagliflozin-bi10773.html
ZINC	ZINC000036520252	http://zinc15.docking.org/substances/ZINC000036520252

PubMed

Title	Date	PubMed
Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.	2015-07	25805666
Empagliflozin for the treatment of type 2 diabetes.	2014-11	25301180
Empagliflozin (Jardiance) for diabetes.	2014-10-13	25296258
Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis.	2014-10	24766495
Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin.	2014-09-28	25260362
Empagliflozin, a sodium glucose co-transporter 2 inhibitor, in the treatment of type 1 diabetes.	2014-06	24746173
Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.	2014-06	24722494
Empagliflozin for the treatment of Type 2 diabetes.	2014-05	24716752
Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.	2014	24991224
Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.	2012-01	21985634
Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus.	2010-01	19892839
From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus.	2009-03	19232040
Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus.	2008-09	18996802

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of JARDIANCE is 10 mg once daily in the morning, taken with or without food. In patients tolerating JARDIANCE, the dose may be increased to 25 mg In patients with volume depletion, correcting this condition prior to initiation of JARDIANCE is recommended. Assessment of renal function is recommended prior to initiation of JARDIANCE and periodically thereafter. JARDIANCE should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m^2. No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m^2. JARDIANCE should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m^2.

Route of Administration: Oral

In Vitro Use Guide

In in vitro experiments empagliflozin is used at a concentration of 100 nM and 500 nM based on recommendations by Boehringer-Ingelheim as these doses effectively and selectively block SGLT2 without significant inhibition of SGLT1.

Name

Type

Language

Empagliflozin

Official Name

English

Empagliflozin [INN]

Preferred Name

English

Empagliflozin [USAN]

Common Name

English

D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-, (1S)-

Common Name

English

TRIJARDY XR COMPONENT EMPAGLIFLOZIN

Brand Name

English

(1S)-1,5-Anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-D-glucitol

Systematic Name

English

BI-10773

Code

English

BI10773

Code

English

Empagliflozin [JAN]

Common Name

English

Empagliflozin [MI]

Common Name

English

GLYXAMBI COMPONENT EMPAGLIFLOZIN

Brand Name

English

Empagliflozin [WHO-DD]

Common Name

English

Jardiance

Brand Name

English

Empagliflozin [ORANGE BOOK]

Common Name

English

Empagliflozin [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-ATC

A10BD20