LEVOVIRIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H12N4O5
Molecular Weight	244.2047
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C1=NN(C=N1)[C@H]2O[C@@H](CO)[C@H](O)[C@@H]2O

InChI

InChIKey=IWUCXVSUMQZMFG-RGDLXGNYSA-N

InChI=1S/C8H12N4O5/c9-6(16)7-10-2-12(11-7)8-5(15)4(14)3(1-13)17-8/h2-5,8,13-15H,1H2,(H2,9,16)/t3-,4-,5-,8-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C8H12N4O5
Molecular Weight	244.2047
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15831782 | https://www.ncbi.nlm.nih.gov/pubmed/10715165 | https://www.ncbi.nlm.nih.gov/pubmed/10770762 | https://www.ncbi.nlm.nih.gov/pubmed/20640834

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 Target ID: GO:0002369 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10715165	Activator 1430
Genome polyprotein 4 Target ID: Q01299 Gene ID: NA Gene Symbol: NA Target Organism: Tick-borne encephalitis virus (strain Hypr) (TBEV) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20640834	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis C 42 Sources: http://www.hepcassoc.org/news/article12.html https://www.ncbi.nlm.nih.gov/pubmed/15831782	Primary		Phase I 428	Unknown Approved Use Unknown
Tick-borne encephalitis 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20640834	Primary		Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.66 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
19.62 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	1500 mg 2 times / day steady-state, oral dose: 1500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.89 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.22 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	1500 mg 2 times / day steady-state, oral dose: 1500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
35.13 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg 2 times / day steady-state, oral dose: 3000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
10.02 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
13.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1.68 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
193.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	1500 mg 2 times / day steady-state, oral dose: 1500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.09 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
275.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	1500 mg 2 times / day steady-state, oral dose: 1500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
371.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg 2 times / day steady-state, oral dose: 3000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
94.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
98 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
9.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	1500 mg 2 times / day steady-state, oral dose: 1500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	1500 mg 2 times / day steady-state, oral dose: 1500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
8.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	3000 mg 2 times / day steady-state, oral dose: 3000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
7.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831782/	750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LEVOVIRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 CYP2E1 882		rCYP1A 2 rCYP2B 2 rCYP3A 3 rCYP4A 2

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
rCYP1A 2	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
rCYP2B 2	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
rCYP3A 3	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no
rCYP4A 2	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/14635270/	no

Sourcing

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
Lab Network	LN00173670	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00173670
Maybridge	HTS11462
MolPort	MolPort-003-699-313	https://www.molport.com/shop/molecule-link/MolPort-003-699-313
MolPort	MolPort-044-812-947	https://www.molport.com/shop/molecule-link/MolPort-044-812-947
PI Chemicals	PI-15844	http://www.pipharm.com/catalog_products/PI-15844.html
Tetrahedron	TS61996	http://www.thsci.com/search.do?q=TS61996
Toronto Research Chemicals	L379000	https://www.trc-canada.com/product-detail/?CatNum=L379000
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
mcule	MCULE-8207297465	https://mcule.com/MCULE-8207297465/

PubMed

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
Past, present, and future hepatitis C treatments.	2004	15346252
Single- and multiple-dose pharmacokinetics of levovirin valinate hydrochloride (R1518) in healthy volunteers.	2005 May	15831782
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
Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy.	2007 Mar	17383421
Effect of ribavirin on the frequency of RNase L cleavage sites within the hepatitis C viral genome.	2010 Mar	19758279
Ribavirin induced hemolysis: a novel mechanism of action against chronic hepatitis C virus infection.	2014 Nov 21	25473172
Prediction of Plasma Concentration-time Profiles of Drugs in Humans from Animals Following Oral Administration: An Allometric Approach.	2016	27903219

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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:42:41 GMT 2023` Edited by `admin` on `Sat Dec 16 09:42:41 GMT 2023`
Record UNII	ZGF0S6S33Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOVIRIN

Common Name

English

ICN-17261

Code

English

1H-1,2,4-TRIAZOLE-3-CARBOXAMIDE, 1-BETA;-L-RIBOFURANOSYL-

Systematic Name

English

Levovirin [WHO-DD]

Common Name

English

Code System Code Type Description

SMS_ID

100000087330