ENTECAVIR ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C12H15N5O3
Molecular Weight	277.2792
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(N=CN2[C@H]3C[C@H](O)[C@@H](CO)C3=C)C(=O)N1

InChI

InChIKey=QDGZDCVAUDNJFG-FXQIFTODSA-N

InChI=1S/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_prntlbl.PDF
Curator's Comment: Description was created based on several resourses, including http://www.drugs.com/monograph/entecavir.html and http://www.drugbank.ca/drugs/DB00442

BARACLUDE® is the tradename for entecavir, a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It inhibits all three steps in the viral replication process. By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity. Entecavir is used for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: http://www.drugbank.ca/drugs/DB00442	Inhibitor 8297		0.004 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis B 57 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_prntlbl.PDF	Primary		Approved 8429	Entecavir Approved Use BARACLUDE (entecavir) is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Launch Date 1.11205443E12

C_max

Value	Dose	Analyte	Population
4.23 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.24 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/	1 mg 1 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ENTECAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.2 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
14.78 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
26.38 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/	1 mg 1 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
27.9 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ENTECAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
129.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
148.89 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/	1 mg 1 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
138.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
87% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ENTECAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 mg 1 times / day steady, oral Highest studied dose Dose: 1 mg, 1 times / day Route: oral Route: steady Dose: 1 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf Page: 6.1	unhealthy, adult n = 183 Health Status: unhealthy Condition: hepatitis B Age Group: adult Sex: unknown Population Size: 183 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf Page: 6.1	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021797s018,021798s019lbl.pdf Page: 6.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111 CYP1A2 1524 CYP2C19 1478 CYP2B6 810 CYP2E1 882 P-gp 1461	CYP 270 UGT enzymes 27 P-gp 1537 MRP4 77 BCRP 561 OCT3 80 OCTN2 50	CYP 76 CYP1A2 701 CYP2C19 293 CYP3A4/5 124 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42.0	inconclusive
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with phenacetin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with S-mephentytoin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with S-mephentytoin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with diclofenac Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with bufuralol Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with p-nitrophenol Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155	no [IC50 >300 uM]	no (co-administration study) Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with testosterone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 42, 154, 155
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 4, 16	no
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 4, 16	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 17.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 17.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 17.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 17.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 17.0	no

Drug as victim

Target	Modality	Activity
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 46.0	likely
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 4, 16	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_biopharmr.PDF Page: 5.0	no
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28627473/	yes
MRP4 77	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28627473/	yes
OCT3 80	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28062543/	yes
OCTN2 50	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28062543/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_BARACLUDE_pharmr.PDF Page: 12, 13, 14

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA001HWV	http://www.aablocks.com/goods/Goods/detail?id=AA001HWV
AEchem Scientific Corp., USA	AE030999	http://www.aechemsc.com/info_products/AE030999.php
AHH Chemical co.,ltd	API-1857	http://www.ahhchemical.com/product/API-1857.html
AHH Chemical co.,ltd	API-1867	http://www.ahhchemical.com/product/API-1867.html
AK Scientific, Inc. (AKSCI)	71985	http://www.aksci.com/item_detail.php?cat=71985
AK Scientific, Inc. (AKSCI)	J90027	http://www.aksci.com/item_detail.php?cat=J90027
Achemtek	0104-042584	http://www.achemtek.com/142217-69-4
Acorn PharmaTech	ACN-040790	http://www.acornpharmatech.com/
Active Biopharma	ABP001043	http://www.activebiopharma.com/142217-69-4
Alfa Chemistry	AP142217694	https://reagents.alfa-chemistry.com/product/entecavir-cas-142217-69-4-4798.html
Ambinter	Amb22167451	http://www.ambinter.com/reference/22167451
Aromalake	LS41110	http://www.aromalake.com/Entecavir-p4151.html
AstaTech, Inc.	27355	http://www.astatechinc.com/CPSResult.php?CRNO=30226
Aurora Fine Chemicals LLC	A17.935.672	http://online.aurorafinechemicals.com/info?ID=A17.935.672
Aurora Fine Chemicals LLC	K16.552.237	http://online.aurorafinechemicals.com/info?ID=K16.552.237
Aurum Pharmatech LLC	S-7388	http://www.Aurumpharmatech.com/Product/ProductDetails/S_7388
AvaChem Scientific	2193	http://www.avachem.com/productSearch.asp?2193
Axon MedChem	3239	https://www.axonmedchem.com/product/3239
BLD Pharm	BD127327	http://www.bldpharm.com/products/142217-69-4.html
Boerchem	BC677668	http://www.boerchem.com/?product_39560.html
CSNpharm	CSN10911	https://www.csnpharm.com/products/entecavir.html
Chem Scene	CS-3160	http://www.chemscene.com/142217-69-4.html
ChemMol	2100032	http://www.chemmol.com/chemmol/2100032.html
ChemMol	30108505	http://www.chemmol.com/chemmol/30108505.html
ChemMol	44009982	http://www.chemmol.com/chemmol/44009982.html
ChemMol	49401413	http://www.chemmol.com/chemmol/49401413.html
ChemMol	81412018	http://www.chemmol.com/chemmol/81412018.html
Chemenu	CM131589	http://www.chemenu.com/products/CM131589
Chemspace	CSSB00016989056	https://chem-space.com/CSSB00016989056
Clearsynth	CS-T-21655	http://www.clearsynth.com/en/CST21655.html
Glentham Life Sciences	GP8732	http://www.glentham.com/products/product/GP8732/
Lab Network	LN00188804	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00188804
Matrix Scientific	90228	https://www.matrixscientific.com/090228.html
MedChem Express	HY-13623	https://www.medchemexpress.com/Entecavir.html
MuseChem	R056572	https://www.musechem.com/product/R056572.html
OChem	9946	http://www.ocheminc.com/index.php?act=psearch&pid=217E694
Oakwood	93332	http://www.oakwoodchemical.com/p-87765-093332.aspx
Parchem	18217	http://www.parchem.com/chemical-supplier-distributor/Entecavir-008217.aspx
Renno Tech	RL01752	http://www.rennotech.com/product_show.asp?id=2001
Sigma-Aldrich	SML1103_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/sml1103?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S527206	http://www.smolecule.com/products/s527206
Specs	AR-270/43507901	http://www.specs.net/enter.php?specsid=AR-270/43507901
Synblock Inc	PB30663	http://www.synblock.com/product/209216-23-9.html
Synchem UG and Co KG	70537	http://www.synchem.de/chemical_Entecavir.html
TCI (Tokyo Chemical Industry)	E0899	http://www.tcichemicals.com/eshop/en/us/commodity/E0899/index.html
THE BioTek	bt-267352	https://www.thebiotek.com/product/inhibitors/bt-267352
THE BioTek	bt-505445	https://www.thebiotek.com/product/others/bt-505445
Tocris	6234	https://www.tocris.com/products/entecavir_6234
VladaChem	VL282225-25mg	https://www.vladachem.com/product.php?products=142217-69-4
Yuhao Chemical	RT5843	http://www.chemyuhao.com/142217-69-4.html
abcr GmbH	AB436292	http://www.abcr.com/shop/en/AB436292
abcr GmbH	AB449610	http://www.abcr.de/shop/en/AB449610
eNovation Chemicals	D371231	http://www.enovationchem.com/productDetails.asp?productID=D371231
eNovation Chemicals	D523180	https://www.enovationchem.com/ProductDetails.asp?ProductID=D523180
eNovation Chemicals	Y0974221	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974221
iChemical	EBD42532	http://www.ichemical.com/products/142217-69-4.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Perspectives for the treatment of hepatitis B virus infections.	1999 Jul	10418752
Nucleoside analogues for chronic hepatitis B.	2001 Dec	11742201
Detection of hepatitis B virus resistance to antivirals.	2001 Jun	11397661
Entecavir (Bristol-Myers Squibb).	2001 May	11569933
Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro.	2002 Aug	12121928
Combination and newer therapies for chronic hepatitis B.	2002 Dec	12472960
Potent efficacy of entecavir (BMS-200475) in a duck model of hepatitis B virus replication.	2002 Jan	11751115
Nucleoside analogues for chronic hepatitis B: antiviral efficacy and viral resistance.	2002 Jul	12135009
Gateways to clinical trials.	2002 Oct	12500432
[Antiviral therapy for chronic viral hepatitis B and C].	2003 Feb	12722317
In vitro activity of potential anti-poxvirus agents.	2003 Jan	12615301
Gateways to clinical trials.	2003 Jan-Feb	12690708
Doctor to patient transmission of hepatitis B virus: implications of HBV DNA levels and potential new solutions.	2003 Oct	14638402
[New approaches in the treatment of hepatitis B].	2004 May 21	15160325
Gateways to clinical trials.	2004 Nov	15632957
Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro.	2004 Oct	15388423
Gateways to clinical trials.	2004 Sep	15538546
Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.	2005 Dec	16168522
Gateways to clinical trials.	2005 Jan-Feb	15834459
Chronic hepatitis B--treatment with nucleoside analogues.	2005 Jul	16108169
Gateways to clinical trials.	2005 May	16082427
New drugs and dosage forms.	2005 May 1	15892212
Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection.	2005 Sep 13	16159399
Introduction to chronic hepatitis B infection.	2006	16448446
Cellular and virological mechanisms of HBV drug resistance.	2006 Feb	16364492

Patents

Sample Use Guides

In Vivo Use Guide

Nucleoside-naive Individuals Oral 0.5 mg once daily. Lamivudine-refractory HBV or known lamivudine- or telbivudine-associated resistance mutations Oral 1 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients were treated with 0.05 ug/mL of Entecavir.

Name

Type

Language

ENTECAVIR ANHYDROUS

Common Name

English

2-AMINO-9-((1S,3R,4S)-4-HYDROXY-3-(HYDROXYMETHYL)-2-METHYLENECYCLOPENTYL)-1,9-DIHYDRO-6H-PURIN-6-ONE

Systematic Name

English

Entecavir [WHO-DD]

Common Name

English

ANHYDROUS ENTECAVIR

Common Name

English

ENTECAVIR [MI]

Common Name

English

6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-((1S,3R,4S)-4-HYDROXY-3-(HYDROXYMETHYL)-2-METHYLENECYCLOPENTYL)-

Systematic Name

English

ENTECAVIR [HSDB]

Common Name

English

entecavir [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C97452