EMTRICITABINE, (±)-

Details

Stereochemistry	RACEMIC
Molecular Formula	C8H10FN3O3S
Molecular Weight	247.247
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)N(C=C1F)[C@@H]2CS[C@H](CO)O2

InChI

InChIKey=XQSPYNMVSIKCOC-NTSWFWBYSA-N

InChI=1S/C8H10FN3O3S/c9-4-1-12(8(14)11-7(4)10)5-3-16-6(2-13)15-5/h1,5-6,13H,2-3H2,(H2,10,11,14)/t5-,6+/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf
Curator's Comment: Description was created based on several sources, including: http://www.emory.edu/news/Releases/emtri/

Emtricitabine was discovered by Emory researchers Dr. Dennis C. Liotta, Dr. Raymond F. Schinazi and Dr. Woo-Baeg Choi and licensed to Triangle Pharmaceuticals by Emory University in 1996. Triangle was acquired by Gilead in 2003. Emtricitabine, marketed by Gilead as Emtriva, was first approved by the U.S. Food and Drug Administration in July 2003 for the treatment of HIV infection in combination with other antiretroviral agents. Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	Inhibitor 8297		0.31 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	Primary		Approved 8429	EMTRIVA Approved Use EMTRIVA is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection. Additional important information regarding the use of EMTRIVA for the treatment of HIV-1 Infection: • EMTRIVA should not be coadministered with ATRIPLA™, TRUVADA®, or Lamivudine-containing products (see WARNINGS). • In treatment-experienced patients, the use of EMTRIVA should be guided by laboratory testing and treatment history (see MICROBIOLOGY). Launch Date 2003

C_max

Value	Dose	Co-administered	Analyte	Population
1.8 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.7 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	5.6 mg/kg 1 times / day steady-state, oral dose: 5.6 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
10 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12.6 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	5.6 mg/kg 1 times / day steady-state, oral dose: 5.6 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	5.6 mg/kg 1 times / day steady-state, oral dose: 5.6 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
96% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021500s010,021896s004lbl.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		EMTRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Co-administed with:: dolutegravir(50 mg) tenofovir disoproxil fumarate(300 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/30420123/	unhealthy, 26 - 42 years n = 717 Health Status: unhealthy Condition: HIV-1 Age Group: 26 - 42 years Sex: M+F Population Size: 717 Sources: https://pubmed.ncbi.nlm.nih.gov/30420123/	Disc. AE: Headache... AEs leading to discontinuation/dose reduction: Headache (grade 2-5, 8 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/30420123/

AEs

AE	Significance	Dose	Population
Headache	grade 2-5, 8 patients Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Co-administed with:: dolutegravir(50 mg) tenofovir disoproxil fumarate(300 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/30420123/	unhealthy, 26 - 42 years n = 717 Health Status: unhealthy Condition: HIV-1 Age Group: 26 - 42 years Sex: M+F Population Size: 717 Sources: https://pubmed.ncbi.nlm.nih.gov/30420123/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 UGT 35	MATE1 135 OCT1 327 OCT2 355 P-gp 1537 BCRP 561 MRP2 205

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-500_Emtriva_BioPharmr_P1.pdf#page=16 Page: 16.0	no
UGT 59	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21500_emtriva_lbl.pdf#page=5 Page: 5.0	no

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27052107/	no
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27052107/	no
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27052107/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27052107/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27052107/	no
MATE1 135	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27052107/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31536	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31536
ChemicalBook	CB5266199	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5266199
MolPort	MolPort-003-986-424	https://www.molport.com/shop/molecule-link/MolPort-003-986-424
ZINC	ZINC000003629271	http://zinc15.docking.org/substances/ZINC000003629271
eMolecules	6719178	https://www.emolecules.com/cgi-bin/more?vid=6719178

PubMed

Title	Date	PubMed
Effect of oral administration of emtricitabine on woodchuck hepatitis virus replication in chronically infected woodchucks.	2000 Jun	10817750
Antiviral beta-L-nucleosides specific for hepatitis B virus infection.	2001	11594678
Antiretroviral activity of emtricitabine, a potent nucleoside reverse transcriptase inhibitor.	2001 Jun	11491420
Gateways to clinical trials.	2002 Dec	12616965
Management of viral hepatitis B.	2002 Feb	12000599
[New management strategies for hepatitis B].	2002 Feb	11938061
Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection.	2002 Jun	12019083
Gateways to clinical trials.	2002 Nov	12616707
Therapy of chronic hepatitis B: current challenges and opportunities.	2002 Nov	12431200
Selection of a hepatitis B virus strain resistant to adefovir in a liver transplantation patient.	2003 Dec	14642631
Treatment of chronic hepatitis B in the human immunodeficiency virus-infected patient: present and future.	2003 Dec 15	14689351
Gateways to clinical trials.	2003 Jan-Feb	12690708
Reproductive toxicology profile of emtricitabine in mice and rabbits.	2003 Jan-Feb	12507664
Gateways to clinical trials.	2003 Jul-Aug	12949633
Gateways to clinical trials. March 2003.	2003 Mar	12731460
Current and future antiviral agents for chronic hepatitis B.	2003 Mar	12615847
FDA notifications. NRTI Emtriva receives FDA approval.	2003 Oct	14686301
Emtricitabine/tenofovir disoproxil fumarate.	2004	15139777
New once-daily HIV combination better tolerated.	2004 Dec	15566325
Emtricitabine: a new nucleoside analogue for once-daily antiretroviral therapy.	2004 Jan	14680453
Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial.	2004 Jul 14	15249567
New drugs of 2003.	2004 Mar-Apr	15098851
Emtricitabine (FTC) for the treatment of HIV infection.	2004 May	15206508
Pharmacologic perspectives for once-daily antiretroviral therapy.	2004 Nov	15479772
Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1.	2004 Oct	15526045
Resistance issues with new nucleoside/nucleotide backbone options.	2004 Sep 1	15319668
New nucleoside/nucleotide backbone options: a review of recent studies.	2004 Sep 1	15319666
Intracellular pharmacology of emtricitabine and tenofovir.	2004 Sep 15	15472830

Patents

Sample Use Guides

In Vivo Use Guide

Emtriva® (emtricitabine) dosage. Adult Patients (18 years of age and older):one 200 mg capsule administered once daily orally (Capsules). 240 mg (24 mL) administered once daily orally (Oral Solution). Pediatric Patients (0–3 months of age): 3 mg/kg administered once daily orally (Oral Solution). Pediatric Patients (3 months through 17 years): 6 mg/kg up to a maximum of 240 mg (24 mL) administered once daily orally (Oral Solution), for children weighing more than 33 kg who can swallow an intact capsule, one 200 mg capsule administered once daily orally (Capsules).

Route of Administration: Oral

In Vitro Use Guide

emtricitabine EC50 0.99 μM (in vitro activity against HIV-2)

Name

Type

Language

EMTRICITABINE, (±)-

Common Name

English

(±)-FTC

Common Name

English

PSI-5004

Code

English

2(1H)-PYRIMIDINONE, 4-AMINO-5-FLUORO-1-((2R,5S)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL)-, REL-

Common Name

English

FTC, DL-

Common Name

English

2',3'-DIDEOXY-5-FLUORO-3'-THIACYTIDINE, DL-

Common Name

English

Code System Code Type Description

DRUG BANK

DB12753