LEVOVIRIN VALINATE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H21N5O6.ClH
Molecular Weight	379.797
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of LEVOVIRIN VALINATE HYDROCHLORIDE

SMILES

Cl.CC(C)[C@H](N)C(=O)OC[C@@H]1O[C@@H]([C@@H](O)[C@H]1O)N2C=NC(=N2)C(N)=O

InChI

InChIKey=BZAMJGAXDMZZKX-JSNLFJDGSA-N

InChI=1S/C13H21N5O6.ClH/c1-5(2)7(14)13(22)23-3-6-8(19)9(20)12(24-6)18-4-16-11(17-18)10(15)21;/h4-9,12,19-20H,3,14H2,1-2H3,(H2,15,21);1H/t6-,7-,8-,9-,12-;/m0./s1

HIDE SMILES / InChI

Description

Levovirin is a guanosine nucleoside analog and the L-enantiomer of ribavirin. It is an investigational drug for the treatment of hepatitis C virus-mediated diseases. Levovirin has a similar immunomodulatory potency to ribavirin in vitro without accumulating in red blood cells or causing hemolytic anemia, a known side effect of ribavirin. Levovirin has been shown to stimulate host immune responses (enhanced Th1 and reduced Th2 cytokine expression). Significantly improved oral absorption of levovirin was achieved following administration of a valine ester prodrug of levovirin R1518. Levovirin was found more potent to inhibit Tick-borne encephalitis virus (TBEV) on the basis of robust binding affinity between protein-drug interactions. This finding may help to understand the nature of helicase and development of specific anti-TBEV therapies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
T cell cytokine production 5	Activator 1,447
Genome polyprotein 5	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis C 42	Primary		Phase I 438	Unknown
Tick-borne encephalitis 3	Primary		Basic research	Unknown

C_max

Value	Dose	Analyte	Population
19.62 μg/mL	1500 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
0.66 μg/mL	3000 mg single, oral	LEVOVIRIN plasma	Homo sapiens
13.65 μg/mL	750 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
28.22 μg/mL	1500 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
0.89 μg/mL	3000 mg single, oral	LEVOVIRIN plasma	Homo sapiens
10.02 μg/mL	750 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
35.13 μg/mL	3000 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
193.1 μg × h/mL	1500 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
1.68 μg × h/mL	3000 mg single, oral	LEVOVIRIN plasma	Homo sapiens
98 μg × h/mL	750 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
275.7 μg × h/mL	1500 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
2.09 μg × h/mL	3000 mg single, oral	LEVOVIRIN plasma	Homo sapiens
94.5 μg × h/mL	750 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
371.7 μg × h/mL	3000 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
9.9 h	1500 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
0.8 h	3000 mg single, oral	LEVOVIRIN plasma	Homo sapiens
15.1 h	750 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
21.1 h	1500 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
0.65 h	3000 mg single, oral	LEVOVIRIN plasma	Homo sapiens
7.7 h	750 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens
8.5 h	3000 mg 2 times / day steady-state, oral	LEVOVIRIN plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252	inhibitor 2,438	inhibitor 2,507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2C19 2,057 CYP2E1 1,060		rCYP1A1/2 2 rCYP2B 5 rCYP3A 4 rCYP4A 2

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP1A2 2,333	inhibitor 4,027	no
CYP2C19 2,141	inhibitor 4,027	no
CYP2C9 2,497	inhibitor 4,027	no
CYP2D6 2,546	inhibitor 4,027	no
CYP2E1 1,146	inhibitor 4,027	no

Showing 1 to 5 of 10 entries

Previous1 2Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
Alfa Chemistry	ACM206269274	http://www.alfa-chemistry.com/search.aspx?q=ACM206269274
BOC Sciences	206269-27-4	http://www.bocsci.com/description.asp?cas=206269-27-4
eMolecules	48882897	https://orderbb.emolecules.com/search/#?query=48882897
eMolecules	50522282	https://orderbb.emolecules.com/search/#?query=50522282
eMolecules	5837679	https://orderbb.emolecules.com/search/#?query=5837679

Showing 1 to 5 of 13 entries

Previous1 2 3Next

PubMed

Show entries

Title	Date	PubMed
The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels.	2000 May	10770762
Inhibitors of the IMPDH enzyme as potential anti-bovine viral diarrhoea virus agents.	2002 Nov	12718406
Transport of levovirin prodrugs in the human intestinal Caco-2 cell line.	2006 Jun	16634069
Hepatitis-C patients have reduced growth hormone (GH) secretion which improves during long-term therapy with pegylated interferon-alpha.	2007 Dec	17662104
Prediction of Plasma Concentration-time Profiles of Drugs in Humans from Animals Following Oral Administration: An Allometric Approach.	2016	27903219

Showing 1 to 5 of 5 entries

Previous1Next

Patents

Sample Use Guides

In Vivo Use Guide

Rat: 180 mg/kg of body weight for 4 weeks

Route of Administration: Oral

In Vitro Use Guide

Levovirin has a very low transport rate through Caco-2 cell monolayers (1.2x10(-7) cm/s). For bi-directional transport studies from basolateral to apical side, 1.25 mL of 20 uM drug solution in pH 7.4 buffer was placed in the basolateral chamber, and 0.5 mL pH 6.5 buffer was put into the apical chamber. There are no significant differences between apical (A) to basolateral (B) and B to A permeability values for levovirin.

Show entries

Name

Type

Language

R-1518

Preferred Name

English

LEVOVIRIN VALINATE HYDROCHLORIDE

Common Name

English

L-VALINE, 5'-ESTER WITH 1-BETA-L-RIBOFURANOSYL-1H-1,2,4-TRIAZOLE-3-CARBOXAMIDE, HYDROCHLORIDE (1:1)

Systematic Name

English

LEVOVIRIN VALINATE HCL

Common Name

English

Showing 1 to 4 of 4 entries

Previous1Next

Show entries

Code System

Code

Type

Description

PUBCHEM

10249157

PRIMARY

FDA UNII

V72F3F078G

PRIMARY

CAS

705930-02-5

PRIMARY

Showing 1 to 3 of 3 entries

Previous1Next

ACTIVE MOIETY


					ZGF0S6S33Q

LEVOVIRIN

SUBSTANCE RECORD


					V72F3F078G

LEVOVIRIN VALINATE HYDROCHLORIDE

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator