Dapagliflozin diproline

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25ClO6.2C5H9NO2
Molecular Weight	639.134
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)[C@@H]1CCCN1.OC(=O)[C@@H]2CCCN2.CCOC3=CC=C(CC4=C(Cl)C=CC(=C4)[C@@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)C=C3

InChI

InChIKey=SAKQQYWVEGDWOE-UFLUWJSBSA-N

InChI=1S/C21H25ClO6.2C5H9NO2/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21;2*7-5(8)4-2-1-3-6-4/h3-8,10,17-21,23-26H,2,9,11H2,1H3;2*4,6H,1-3H2,(H,7,8)/t17-,18-,19+,20-,21+;2*4-/m100/s1

HIDE SMILES / InChI

Molecular Formula	C21H25ClO6
Molecular Weight	408.873
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C5H9NO2
Molecular Weight	115.1305
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s003lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27042132

Dapagliflozin (trade name Farxiga in the U.S. and Forxiga in the EU and Russia) is a drug of the gliflozin class, developed by Bristol-Myers Squibb in partnership with AstraZeneca. Farxiga is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium/glucose cotransporter 2 25 Target ID: CHEMBL3884 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s003lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/23657801	Inhibitor 8297		1.16 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s003lbl.pdf	Primary		Approved 8429	FARXIGA Approved Use FARXIGA (dapagliflozin) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Launch Date 2014

C_max

Value	Dose	Analyte	Population
154 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	10 mg single, oral dose: 10 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
24.6 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	2.5 mg single, oral dose: 2.5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
49 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	5 mg single, oral dose: 5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
118 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	10 mg single, oral dose: 10 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
24.8 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	2.5 mg single, oral dose: 2.5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
48.4 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	5 mg single, oral dose: 5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
119 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED
116 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
208 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	5 mg single, oral dose: 5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
612 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	10 mg single, oral dose: 10 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
95.8 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	2.5 mg single, oral dose: 2.5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
105 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	2.5 mg single, oral dose: 2.5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
232 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	5 mg single, oral dose: 5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
658 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	10 mg single, oral dose: 10 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN 3-O-GLUCURONIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:
189 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	5 mg single, oral dose: 5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
418 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	10 mg single, oral dose: 10 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
92.3 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	2.5 mg single, oral dose: 2.5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
101 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	2.5 mg single, oral dose: 2.5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
199 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	5 mg single, oral dose: 5 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
427 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01525238	10 mg single, oral dose: 10 mg route of administration: oral experiment type: single co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: unhealthy age: Children sex: food status:
506 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED
368 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	DAPAGLIFLOZIN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
15.77 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DAPAGLIFLOZIN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED
3 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		DAPAGLIFLOZIN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
10 mg single, oral Highest studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27291448	unhealthy, 14.6 years (range: 11–17) n = 8 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 14.6 years (range: 11–17) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/27291448	Other AEs: Abdominal pain upper, Back pain... Other AEs: Abdominal pain upper (12.5%) Back pain (12.5%) Nausea (12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/27291448
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30653152	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/30653152	Disc. AE: Ketoacidosis... AEs leading to discontinuation/dose reduction: Ketoacidosis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30653152
50 mg single, oral Highest studied dose Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21226818	healthy, 24 years (range: 20–45 years years) n = 8 Health Status: healthy Age Group: 24 years (range: 20–45 years years) Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21226818	Sources: https://pubmed.ncbi.nlm.nih.gov/21226818
20 mg 1 times / day steady, oral Highest studied dose Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21226818	unhealthy, 62 years (range: 20 - 70 years) n = 12 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 62 years (range: 20 - 70 years) Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/21226818	Other AEs: Protein urine present... Other AEs: Protein urine present (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21226818
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	Other AEs: Coronary artery disease, Gastritis... Other AEs: Coronary artery disease (serious, 1 patient) Gastritis (serious, 1 patient) Lung infection (serious, 1 patient) Acidosis (serious, 1 patient) Osteoarthritis (serious, 1 patient) Colorectal cancer (serious, 1 patient) Syncope (serious, 1 patient) Ectopic pregnancy (serious, 1 patient) Calculus ureteric (serious, 1 patient) Hydronephrosis (serious, 1 patient) Hyperlipidaemia (below serious, 31 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02113241	unhealthy n = 12 Health Status: unhealthy Condition: Metabolic Syndrome Population Size: 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02113241	Other AEs: Urinary infection... Other AEs: Urinary infection (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02113241
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02371187	unhealthy n = 18 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 18 Sources: https://clinicaltrials.gov/ct2/show/NCT02371187	Other AEs: Muscle soreness... Other AEs: Muscle soreness (below serious, 8 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT02371187
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	unhealthy n = 22 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	Other AEs: Increased urinary frequency, Vaginal itching... Other AEs: Increased urinary frequency (below serious, 3 patients) Vaginal itching (below serious, 2 patients) Nausea (below serious, 1 patient) Dry mouth (below serious, 2 patients) Urinary tract infection (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02613897
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02700334	unhealthy n = 12 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02700334	Other AEs: Urinary tract infection, Low back pain... Other AEs: Urinary tract infection (below serious, 2 patients) Low back pain (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02700334
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT03006471	unhealthy n = 15 Health Status: unhealthy Condition: PreDiabetes Population Size: 15 Sources: https://clinicaltrials.gov/ct2/show/NCT03006471	Other AEs: Vaginal infection, Urinary tract infections... Other AEs: Vaginal infection (below serious, 3 patients) Urinary tract infections (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT03006471
2.5 mg 1 times / day steady, oral Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00736879	unhealthy n = 74 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 74 Sources: https://clinicaltrials.gov/ct2/show/NCT00736879	Other AEs: Uterine leiomyoma, Pneumonia... Other AEs: Uterine leiomyoma (serious, 1 patient) Pneumonia (serious, 1 patient) Pharyngitis (below serious, 4 patients) Dizziness (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00736879

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C19 1478 CYP2C8 911 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT2 647 P-gp 1461	CYP 270 CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2E1 667 CYP3A5 395 OAT1 326 OAT3 339 OATP1B1 406 OATP1B3 350 OCT2 355 P-gp 1537 UGT1A9 380	CYP1A2 701 CYP2B6 547 CYP3A4/5 124 PXR 9

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no [IC50 >45 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no [IC50 >45 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no [IC50 >45 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no [IC50 >45 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no [IC50 >45 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 67	no [IC50 >45 uM]	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 67
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 67	no [IC50 >45 uM]	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 67
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 67	no [IC50 >45 uM]	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 67
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64, 67	no [IC50 >57.6 uM]	no (co-administration study) Comment: dapagliflozin does not demonstrate any ability to inhibit P-gp mediated efflux of digoxin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64, 67
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64.0	no
PXR 46	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64, 67	no	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64, 67
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 91.0	weak [IC50 >45 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64, 67	yes [IC50 33 uM]	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 64, 67
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	yes [IC50 69 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	yes [IC50 8 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 67.0	minor
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	no	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted from clinical pharmacology review p67 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 68.0	weak
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	yes
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	yes
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	yes
CYP3A5 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63.0	yes
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 65	yes	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 65
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 65	yes	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 65
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 65	yes	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 63, 65
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0	yes	no (co-administration study) Comment: no clinically meaningful drug-drug interaction observed in the all the DDI studies conducted from clinical pharmacology review p67 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000PharmR.pdf Page: 29.0
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 65.0	yes	unlikely (co-administration study) Comment: coadministration of mefenamic acid showed slight increase in dapagliflozin exposure; the increase in exposure does not warrant any dose adjustment Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000ClinPharmR.pdf Page: 65.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85078	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85078
ChemicalBook	CB91011730	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB91011730
MolPort	MolPort-009-682-875	https://www.molport.com/shop/molecule-link/MolPort-009-682-875
Selleck Chemicals	Dapagliflozin	http://www.selleckchem.com/products/Dapagliflozin.html
ZINC	ZINC000003819138	http://zinc15.docking.org/substances/ZINC000003819138
eMolecules	32278060	https://www.emolecules.com/cgi-bin/more?vid=32278060

PubMed

Title	Date	PubMed
Molecule of the month. Dapagliflozin.	2007 Dec	18301798
Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats.	2008 Jun	18356408
Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.	2008 Mar 13	18260618
Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus.	2008 Sep	18996802
Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes.	2009 Apr	19114612
Gateways to clinical trials.	2009 Dec	20140276
Dapagliflozin, an oral sodium glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus.	2009 Dec	19943222
Dapagliflozin for the treatment of type 2 diabetes.	2009 Jul	19584379
Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications.	2009 Jun	19357717
Gateways to clinical trials.	2009 Mar	19455266
Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects.	2009 May	19129748
Gateways to clinical trials.	2009 Oct	19967103
Dapagliflozin: where does it fit in the treatment of type 2 diabetes?	2009 Oct	19735212
A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment.	2009 Sep	19528367
A novel strategy for the treatment of diabetes mellitus - sodium glucose co-transport inhibitors.	2010 Dec	22558567
Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members.	2010 Dec	22127746
Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes.	2010 Dec	22127745
(5-Bromo-2-methyl-phen-yl)(4-eth-oxy-phen-yl)methanone.	2010 Jul 17	21588347
Gateways to clinical trials.	2010 Jul-Aug	20852754
Neuropathy, retinopathy, and glucose-lowering treatments.	2010 Jun	20508223
In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans.	2010 Mar	19996149
Sodium-glucose co-transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus.	2010 Mar 5	20205482
The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats.	2010 Nov	20880347

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose is 5 mg once daily, taken in the morning, with or without food. Dose can be increased to 10 mg once daily in patients tolerating FARXIGA who require additional glycemic control.

Route of Administration: Oral

In Vitro Use Guide

The IC50 values of dapagliflozin for hSGLT2 and hSGLT1 determined using 1-NBDG were 1.86 nM and 880 nM

Substance Class	Chemical Created by `admin` on `Sat Dec 16 19:27:32 GMT 2023` Edited by `admin` on `Sat Dec 16 19:27:32 GMT 2023`
Record UNII	Q54R5GG9QQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Dapagliflozin diproline

Common Name

English

Dapagliflozin L-prolinate

Common Name

English

Dapagliflozin bis L-proline [WHO-DD]

Common Name

English

Dapagliflozin bis L-proline

Common Name

English

L-Proline, compd. with (1S)-1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol (2:1)

Systematic Name

English

Code System Code Type Description

FDA UNII

Q54R5GG9QQ

Created by admin on Sat Dec 16 19:27:32 GMT 2023 , Edited by admin on Sat Dec 16 19:27:32 GMT 2023

PRIMARY

PUBCHEM

25032144

Created by admin on Sat Dec 16 19:27:32 GMT 2023 , Edited by admin on Sat Dec 16 19:27:32 GMT 2023

PRIMARY

CAS

960404-62-0

Created by admin on Sat Dec 16 19:27:32 GMT 2023 , Edited by admin on Sat Dec 16 19:27:32 GMT 2023

PRIMARY

Related Record Type Details


					1ULL0QJ8UC

DAPAGLIFLOZIN

PARENT -> SALT/SOLVATE

Amount:


					9DLQ4CIU6V

PROLINE

PARENT -> SALT/SOLVATE

Amount:

AE	Significance	Dose	Population
Abdominal pain upper	12.5%	10 mg single, oral Highest studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27291448	unhealthy, 14.6 years (range: 11–17) n = 8 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 14.6 years (range: 11–17) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/27291448
Back pain	12.5%	10 mg single, oral Highest studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27291448	unhealthy, 14.6 years (range: 11–17) n = 8 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 14.6 years (range: 11–17) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/27291448
Nausea	12.5%	10 mg single, oral Highest studied dose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27291448	unhealthy, 14.6 years (range: 11–17) n = 8 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 14.6 years (range: 11–17) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/27291448
Ketoacidosis	1 patient Disc. AE	10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30653152	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/30653152
Protein urine present	2 patients	20 mg 1 times / day steady, oral Highest studied dose Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21226818	unhealthy, 62 years (range: 20 - 70 years) n = 12 Health Status: unhealthy Condition: type 2 diabetes mellitus Age Group: 62 years (range: 20 - 70 years) Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/21226818
Hyperlipidaemia	below serious, 31 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Acidosis	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Calculus ureteric	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Colorectal cancer	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Coronary artery disease	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Ectopic pregnancy	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Gastritis	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Hydronephrosis	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Lung infection	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Osteoarthritis	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Syncope	serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02096705	unhealthy n = 139 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 139 Sources: https://clinicaltrials.gov/ct2/show/NCT02096705
Urinary infection	below serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02113241	unhealthy n = 12 Health Status: unhealthy Condition: Metabolic Syndrome Population Size: 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02113241
Muscle soreness	below serious, 8 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02371187	unhealthy n = 18 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 18 Sources: https://clinicaltrials.gov/ct2/show/NCT02371187
Nausea	below serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	unhealthy n = 22 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02613897
Urinary tract infection	below serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	unhealthy n = 22 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02613897
Dry mouth	below serious, 2 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	unhealthy n = 22 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02613897
Vaginal itching	below serious, 2 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	unhealthy n = 22 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02613897
Increased urinary frequency	below serious, 3 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02613897	unhealthy n = 22 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02613897
Low back pain	below serious, 1 patient	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02700334	unhealthy n = 12 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02700334
Urinary tract infection	below serious, 2 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02700334	unhealthy n = 12 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02700334
Urinary tract infections	below serious, 2 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT03006471	unhealthy n = 15 Health Status: unhealthy Condition: PreDiabetes Population Size: 15 Sources: https://clinicaltrials.gov/ct2/show/NCT03006471
Vaginal infection	below serious, 3 patients	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT03006471	unhealthy n = 15 Health Status: unhealthy Condition: PreDiabetes Population Size: 15 Sources: https://clinicaltrials.gov/ct2/show/NCT03006471
Pharyngitis	below serious, 4 patients	2.5 mg 1 times / day steady, oral Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00736879	unhealthy n = 74 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 74 Sources: https://clinicaltrials.gov/ct2/show/NCT00736879
Dizziness	below serious, 5 patients	2.5 mg 1 times / day steady, oral Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00736879	unhealthy n = 74 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 74 Sources: https://clinicaltrials.gov/ct2/show/NCT00736879
Pneumonia	serious, 1 patient	2.5 mg 1 times / day steady, oral Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00736879	unhealthy n = 74 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 74 Sources: https://clinicaltrials.gov/ct2/show/NCT00736879
Uterine leiomyoma	serious, 1 patient	2.5 mg 1 times / day steady, oral Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00736879	unhealthy n = 74 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 74 Sources: https://clinicaltrials.gov/ct2/show/NCT00736879

Details

SMILES

InChI

DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s003lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27042132

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s003lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27042132

C_max

T_1/2

Drug as perpetrator