MARIBAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H19Cl2N3O4
Molecular Weight	376.235
Optical Activity	( - )
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC(C)NC1=NC2=C(C=C(Cl)C(Cl)=C2)N1[C@H]3O[C@@H](CO)[C@H](O)[C@@H]3O

InChI

InChIKey=KJFBVJALEQWJBS-XUXIUFHCSA-N

InChI=1S/C15H19Cl2N3O4/c1-6(2)18-15-19-9-3-7(16)8(17)4-10(9)20(15)14-13(23)12(22)11(5-21)24-14/h3-4,6,11-14,21-23H,5H2,1-2H3,(H,18,19)/t11-,12-,13-,14-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C15H19Cl2N3O4
Molecular Weight	376.235
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

Maribavir (previously known as 1263W94) is a novel benzimidazole riboside compound. This drug was in phase III of clinical trial for the prevention of cytomegalovirus (CMV) infections in transplant patients, sponsored by ViroPharma. However, drug failed to demonstrate a higher efficacy rate than the placebo. Maribavir has activity against cytomegalovirus and Epstein-Barr virus (EBV), but not against other human herpesviruses. Maribavir’s mechanism of action is unique and is complex compared to the currently approved antivirals for CMV. Maribavir inhibits the viral UL97 kinase rather than the viral DNA polymerase. The UL97 kinase is important for viral DNA elongation, DNA packaging, and nuclear egress of encapsidated viral DNA. In addition, maribavir inhibits the EBV DNA polymerase processivity factor (BMRF1), reduces the level of certain EBV glycoproteins, and inhibits viral transcription. However, future work will be designed to address the interaction of MBV and BGLF4 and to evaluate the mechanisms through which maribavir downregulates viral transcripts. BGLF4 belongs to the family of conserved herpesvirus PKs, which includes HCMV UL97, HSV UL13, and HSV US3. Maribavir does need to be phosphorylated for its activity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine protein kinase UL97 1	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cytomegalovirus infection 6	Preventing		Phase III 665	Unknown

C_max

Value	Dose	Analyte	Population
17.2 μg/mL	400 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
2.66 μg/mL	50 mg single, oral	MARIBAVIR plasma	Homo sapiens
3.32 μg/mL	100 mg single, oral	MARIBAVIR plasma	Homo sapiens
7.45 μg/mL	200 mg single, oral	MARIBAVIR plasma	Homo sapiens
16.68 μg/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
26.39 μg/mL	800 mg single, oral	MARIBAVIR plasma	Homo sapiens
48.81 μg/mL	1600 mg single, oral	MARIBAVIR plasma	Homo sapiens
3.783 μg/mL	100 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
4.371 μg/mL	100 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
8.154 μg/mL	200 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
6.999 μg/mL	200 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
18.102 μg/mL	400 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
19.189 μg/mL	400 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
30.551 μg/mL	600 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
33.499 μg/mL	600 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
35.366 μg/mL	900 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
43.532 μg/mL	900 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
34.005 μg/mL	1200 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
43.905 μg/mL	1200 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
11.4 μg/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
15.9 μg/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
20.98 μg/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
21.88 μg/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
20.34 μg/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
12.72 μg/mL	200 mg single, oral	MARIBAVIR plasma	Homo sapiens
9.45 μg/mL	200 mg single, oral	MARIBAVIR plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
128 μg × h/mL	400 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
10.77 μg × h/mL	50 mg single, oral	MARIBAVIR plasma	Homo sapiens
16.31 μg × h/mL	100 mg single, oral	MARIBAVIR plasma	Homo sapiens
34.16 μg × h/mL	200 mg single, oral	MARIBAVIR plasma	Homo sapiens
97.8 μg × h/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
183.05 μg × h/mL	800 mg single, oral	MARIBAVIR plasma	Homo sapiens
436.75 μg × h/mL	1600 mg single, oral	MARIBAVIR plasma	Homo sapiens
12.79 μg × h/mL	100 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
17.2 μg × h/mL	100 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
28.79 μg × h/mL	200 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
26.73 μg × h/mL	200 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
55.49 μg × h/mL	400 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
77.42 μg × h/mL	400 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
122.01 μg × h/mL	600 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
126.76 μg × h/mL	600 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
154.82 μg × h/mL	900 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
229.92 μg × h/mL	900 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
206.05 μg × h/mL	1200 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
249 μg × h/mL	1200 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
85.6 μg × h/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
99 μg × h/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
138.3 μg × h/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
127.6 μg × h/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
122.6 μg × h/mL	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
78.6 μg × h/mL	200 mg single, oral	MARIBAVIR plasma	Homo sapiens
62.3 μg × h/mL	200 mg single, oral	MARIBAVIR plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
4.32 h	400 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
3.28 h	50 mg single, oral	MARIBAVIR plasma	Homo sapiens
3.01 h	100 mg single, oral	MARIBAVIR plasma	Homo sapiens
3.64 h	200 mg single, oral	MARIBAVIR plasma	Homo sapiens
3.91 h	400 mg single, oral	MARIBAVIR plasma	Homo sapiens
4.04 h	800 mg single, oral	MARIBAVIR plasma	Homo sapiens
4.8 h	1600 mg single, oral	MARIBAVIR plasma	Homo sapiens
5.07 h	100 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
5.67 h	100 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
4.55 h	200 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
3.78 h	200 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
5.86 h	400 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
5.37 h	400 mg 3 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
5.23 h	600 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
6.1 h	600 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
5.04 h	900 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
4.73 h	900 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
6.39 h	1200 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens
5.83 h	1200 mg 2 times / day multiple, oral	MARIBAVIR plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%			MARIBAVIR plasma	Homo sapiens
2%			MARIBAVIR plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1200 mg 2 times / day steady-state, oral Highest studied dose	unhealthy, ADULT	Disc. AE: death... Other AEs: Dysgeusia, Nausea...
400 mg single, oral Studied dose	healthy, ADULT	Other AEs: Dysgeusia...
400 mg single, oral Studied dose	healthy, ADULT	Other AEs: Dysgeusia, Headache...
400 mg 2 times / day steady-state, oral Studied dose	unhealthy, ADULT	Disc. AE: death... Other AEs: Dysgeusia, Nausea...
800 mg 2 times / day steady-state, oral Studied dose	unhealthy, ADULT	Disc. AE: death... Other AEs: Dysgeusia, Nausea...

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AEs

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AE	Significance	Dose	Population
Depression	1 pt	1200 mg 2 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Anemia	10 patients	1200 mg 2 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Diarrhea	10 patients	1200 mg 2 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Vomiting	11 patient	1200 mg 2 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Nausea	14 patients	1200 mg 2 times / day steady-state, oral Highest studied dose	unhealthy, ADULT

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PubMed

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Title	Date	PubMed
Development of novel benzimidazole riboside compounds for treatment of cytomegalovirus disease.	1999	10549385
Inhibition of Epstein-Barr virus replication by a benzimidazole L-riboside: novel antiviral mechanism of 5, 6-dichloro-2-(isopropylamino)-1-beta-L-ribofuranosyl-1H-benzimidazole.	1999 Sep	10438815
Synthesis and antiviral evaluation of halogenated beta-D- and -L-erythrofuranosylbenzimidazoles.	2000 Jun 15	10882374
Inhibition of human cytomegalovirus replication by benzimidazole nucleosides involves three distinct mechanisms.	2004 Oct	15388453
In vitro activity and mechanism of action of methylenecyclopropane analogs of nucleosides against herpesvirus replication.	2005 Mar	15728900

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Patents

Sample Use Guides

In Vivo Use Guide

100 mg twice daily for up to 12 weeks

Route of Administration: Oral

In Vitro Use Guide

Maribavir (MBV) may be linked to indirect effects on the transcription of Epstein-Barr virus (EBV) genes through the interaction of BGLF4 with multiple viral proteins. It was examined the effects of MBV and acyclovir (ACV) on the expression of the early (EA-D) and the late (gp125 and gp350) viral proteins by immunofluorescence staining. EA-D was detected in the nucleus, while both gp125 and gp350 were detected in the cytoplasm. MBV (20 μM) reduced the number of cells expressing EA-D by about 50% and almost eliminated the expression of gp125 and gp350 . It was revealed the potent inhibitory effect of MBV on the phosphorylation of EA-D during lytic infection and the lack of such an effect produced by ACV. Both drugs inhibited the expression of the two late viral glycoproteins, but MBV had a considerably greater effect, probably due to its greater antiviral potency.

Substance Class	Chemical
Record UNII	PTB4X93HE1
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

MARIBAVIR

Official Name

English

LIVTENCITY

Preferred Name

English

maribavir [INN]

Common Name

English

1H-BENZIMIDAZOL-2-AMINE, 5,6-DICHLORO-N-(1-METHYLETHYL)-1-.BETA.-L-RIBOFURANOSYL-

Systematic Name

English

1263-W-94

Code

English

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Classification Tree

Code System

Code

Other antivirals

WHO-VATC

QJ05AX10

Antimetabolite

NCI_THESAURUS

C1556

Designated

FDA ORPHAN DRUG

229906

Anti-Infective Agent

NCI_THESAURUS

C281

Designated/Approved

FDA ORPHAN DRUG

332210

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Code System

Code

Type

Description

RXCUI

2586068

PRIMARY

MESH

C400401

PRIMARY

DRUG BANK

DB06234

PRIMARY

DAILYMED

PTB4X93HE1

PRIMARY

PUBCHEM

471161

PRIMARY

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					7COI029E6K

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TARGET ORGANISM->INHIBITOR

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N-nitroso-maribavir

IMPURITY -> PARENT

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					PTB4X93HE1

MARIBAVIR

ACTIVE MOIETY

Amount:

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound