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(CC3=CC=C(O[C@H]4CCOC4)C=C3)=C(Cl)C=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 2778		3.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204629s000lbl.pdf	Secondary		Approved 8429	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 1587 inducer 781	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 P-gp 1461 OAT1 599 OAT3 642 OCT2 647 OATP1B1 788 OATP1B3 706 MRP2 383 BCRP 699 OATP2B1 123 UGT1A1 204 UGT1A3 84 UGT1A8 36 UGT1A9 116 UGT2B7 146	OAT3 339 OATP1B1 406 OATP1B3 350 OAT1 326 OCT2 355 UGT2B7 389 UGT1A3 422 UGT1A8 283 UGT1A9 380 CYP3A 191	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no [IC50 >1000 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no [IC50 >1000 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	no [IC50 >150 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT1A3 93	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT1A8 48	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT1A9 121	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf#page=14 Page: 14.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 114.1 uM]
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 1399 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 295 uM]
OATP2B1 126	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 45.2 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	weak [IC50 58.6 uM]
OATP1B1 803	inhibitor 3277 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 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000PharmR.pdf#page=33 Page: 33.0	yes
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	yes
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	yes
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	yes
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
UGT1A8 283	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
UGT2B7 389	substrate 3367 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
From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus.	2009 Mar	19232040

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 COMPONENT OF GLYXAMBI

Brand 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)-OXAN-3-YL)OXY)PHENYL)METHYL)PHENYL)-D-GLUCITOL

Common Name

English

BI-10773

Code

English

EMPAGLIFLOZIN COMPONENT OF TRIJARDY XR

Brand Name

English

BI10773

Code

English

EMPAGLIFLOZIN COMPONENT OF SYNJARDY

Brand Name

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 [INN]

Common Name

English

EMPAGLIFLOZIN [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-ATC

A10BD20