BALAPIRAVIR

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H30N6O8
Molecular Weight	494.4983
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

CC(C)C(=O)OC[C@]1(O[C@H]([C@H](OC(=O)C(C)C)[C@@H]1OC(=O)C(C)C)N2C=CC(N)=NC2=O)N=[N+]=[N-]

InChI

InChIKey=VKXWOLCNTHXCLF-DXEZIKHYSA-N

InChI=1S/C21H30N6O8/c1-10(2)17(28)32-9-21(25-26-23)15(34-19(30)12(5)6)14(33-18(29)11(3)4)16(35-21)27-8-7-13(22)24-20(27)31/h7-8,10-12,14-16H,9H2,1-6H3,(H2,22,24,31)/t14-,15+,16-,21-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C21H30N6O8
Molecular Weight	494.4983
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description

R1479 (4′-azidocytidine) is a specific inhibitor of hepatitis C virus (HCV) replication. 4′-azidocytidine triphosphate is an inhibitor of native HCV replicase and recombinant HCV polymerase (NS5B). Balapiravir (R1626) is the tri-isobutyrate ester prodrug of R1479 under clinical development to improve exposure of R1479 upon oral administration.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14	Inhibitor 8,504		40.0 nM [Ki]
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14	Inhibitor 8,504		40.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Hepatitis C 42	Primary	Phase II 1,147	Unknown
Dengue virus infection 12	Primary	Phase I 438	Unknown
Hepatitis C 42	Primary	Phase I 438	Unknown

C_max

Value	Dose	Analyte	Population
16.54 μM	1500 mg single, oral	R-1479 serum	Homo sapiens
23.86 μM	3000 mg single, oral	R-1479 serum	Homo sapiens
9.9 mg/L	1500 mg 2 times / day steady-state, oral	R-1479 plasma	Homo sapiens
4 μg/mL	500 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens
10 μg/mL	1500 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens
15 μg/mL	3000 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens
24 μg/mL	4500 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens
16.54 μg/mL	1500 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens
23.86 μg/mL	3000 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
110.56 μM × h	1500 mg single, oral	R-1479 serum	Homo sapiens
167.04 μM × h	3000 mg single, oral	R-1479 serum	Homo sapiens
63.3 mg × h/L	1500 mg 2 times / day steady-state, oral	R-1479 plasma	Homo sapiens
110.56 μg × h/mL	1500 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens
167.04 μg × h/mL	3000 mg 2 times / day multiple, oral	R-1479 plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.62 h	500 mg 2 times / day multiple, oral		R-1479 plasma	Homo sapiens
5.87 h	4500 mg 2 times / day multiple, oral		R-1479 plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
4500 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT	Disc. AE: Nausea, Vomiting...
1500 mg 2 times / week multiple, oral Studied dose	unhealthy, ADULT	Disc. AE: Eye disorders...

Showing 1 to 2 of 2 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Vomiting	11.1% Disc. AE	4500 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Nausea	grade 3, 11.1% Disc. AE	4500 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Eye disorders	grade 3, 7% Disc. AE	1500 mg 2 times / week multiple, oral Studied dose	unhealthy, ADULT

Showing 1 to 3 of 3 entries

Previous1Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 29	P-gp 2,052 CYPs 33 UCK1 3	CYPs 17

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
CYPs 35	inducer 1,966	no
CYPs 35	inhibitor 4,027	no

Showing 1 to 2 of 2 entries

Previous1Next

Drug as victim

Show entries

Target	Modality	Activity
CYPs 33	substrate 4,014	no
P-gp 2,052	substrate 4,014	no
UCK1 3	substrate 4,014	yes

Showing 1 to 3 of 3 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00DEJW	https://www.1pchem.com/search?query=1P00DEJW
Achemo Scientific Limited	AC-75364	http://www.achemo.com/search/?Keyword=AC-75364
AK Scientific	3995AH	https://aksci.com/item_detail.php?cat=3995AH
eMolecules	44811737	https://orderbb.emolecules.com/search/#?query=44811737
KeyOrganics	AS-56761	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56761

Showing 1 to 5 of 13 entries

Previous1 2 3Next

PubMed

Show entries

Title	Date	PubMed
2'-deoxy-4'-azido nucleoside analogs are highly potent inhibitors of hepatitis C virus replication despite the lack of 2'-alpha-hydroxyl groups.	2008 Jan 25	18003608

Showing 1 to 1 of 1 entries

Previous1Next

Patents

Sample Use Guides

In Vivo Use Guide

The phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in hepatitis C genotype 1 patients. Treatment-naive genotype 1 patients were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.

Route of Administration: Oral

In Vitro Use Guide

R1479 (4'-azidocytidine) is a specific inhibitor of HCV replication in the HCV subgenomic replicon system (IC(50) = 1.28 microM). R1479 showed no effect on cell viability or proliferation of HCV replicon or Huh-7 cells at concentrations up to 2 mM.

Substance Class	Chemical
Record UNII	VOT0LP7I9K
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

R-1626

Preferred Name

English

BALAPIRAVIR

Official Name

English

R1626

Code

English

Balapiravir [WHO-DD]

Common Name

English

RO-4588161

Code

English

Showing 1 to 5 of 10 entries

Previous1 2Next

Show entries

Classification Tree

Code System

Code

Anti-Infective Agent

NCI_THESAURUS

C281

Enzyme Inhibitor

NCI_THESAURUS

C25995

Showing 1 to 2 of 2 entries

Previous1Next

Show entries

Code System

Code

Type

Description

DRUG BANK

DB12283

PRIMARY

CAS

690270-29-2

PRIMARY

WIKIPEDIA

Balapiravir

PRIMARY

NCI_THESAURUS

C87439

PRIMARY

INN

8977

PRIMARY

Showing 1 to 5 of 13 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					C860V13650

BALAPIRAVIR HYDROCHLORIDE

SALT/SOLVATE -> PARENT

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

Show entries

Related Record

Type

Details


					M71RA9DMGJ

R-1479

METABOLITE ACTIVE -> PRODRUG

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

Show entries

Related Record

Type

Details


					M71RA9DMGJ

R-1479

ACTIVE MOIETY

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator