AMDOXOVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H12N6O3
Molecular Weight	252.23
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(N=CN2[C@H]3CO[C@@H](CO)O3)C(N)=N1

InChI

InChIKey=RLAHNGKRJJEIJL-RFZPGFLSSA-N

InChI=1S/C9H12N6O3/c10-7-6-8(14-9(11)13-7)15(3-12-6)4-2-17-5(1-16)18-4/h3-5,16H,1-2H2,(H4,10,11,13,14)/t4-,5-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15351346
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800004771

Amdoxovir is a guanosine analogue nucleoside reverse transcriptase inhibitor that is active in vitro against both HIV-1 and HBV. It is deaminated intracellularly by adenosine deaminase to dioxolane guanine (DXG). DXG-triphosphate, the active form of the drug, has greater activity than DAPD-triphosphate. Amdoxovir is under development (phase II study) for the treatment of HIV infection. Five subjects demonstrated lens opacities during the study, although baseline evaluations were not performed. Clinical studies of amdoxovir are currently on hold pending additional safety data.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
DNA polymerase/reverse transcriptase 10 Target ID: CHEMBL2362994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10760047	Inhibitor 8297	0.61 µM [IC50]
Adenosine deaminase 13 Target ID: CHEMBL2966 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Substrate 661
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959 \| http://adisinsight.springer.com/drugs/800004771	Inhibitor 8297	0.019 µM [Ki]
DNA polymerase beta 5 Target ID: CHEMBL2392 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Inhibitor 8297	32.0 µM [Ki]
DNA polymerase alpha subunit 9 Target ID: CHEMBL1828 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Inhibitor 8297	78.0 µM [Ki]
DNA polymerase gamma subunit 1 2 Target ID: CHEMBL2732 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Inhibitor 8297	4.3 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16964830	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
499 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20038617	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		AMDOXOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1545 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/20038617	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		1,3-DIOXOLANE GUANOSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1326 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20038617	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		AMDOXOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6834 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/20038617	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		1,3-DIOXOLANE GUANOSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20038617	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		AMDOXOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17.6 h REVIEW https://pubmed.ncbi.nlm.nih.gov/20038617	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		1,3-DIOXOLANE GUANOSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16184030	unhealthy n = 8 Health Status: unhealthy Condition: HIV infection Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/16184030	Sources: https://pubmed.ncbi.nlm.nih.gov/16184030

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	145514-04-1	http://www.bocsci.com/description.asp?cas=145514-04-1
Compound Cloud	124088
MuseChem	M091480	https://www.musechem.com/product/M091480.html
eMolecules	109867526	https://orderbb.emolecules.com/search/#?query=109867526
eMolecules	76746369	https://orderbb.emolecules.com/search/#?query=76746369

PubMed

Title	Date	PubMed
Perspectives for the treatment of hepatitis B virus infections.	1999 Jul	10418752
Mechanism of action and in vitro activity of 1',3'-dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants.	1999 Oct	10508010
In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine.	2000 Jul	10858331
Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine.	2001 Jan	11120959
In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.	2001 Sep	11502520
Gateways to clinical trials. March 2003.	2003 Mar	12731460
Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses.	2003 May 23	12651859
In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1.	2004 Nov	15504868
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.	2004 Sep	15183346
Gateways to clinical trials.	2005 Jun	16082422
Emerging anti-HIV drugs.	2005 May	15934866
Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine.	2005 May	15855524
Gateways to clinical trials.	2007 Dec	18200333
Determination of 19 antiretroviral agents in pharmaceuticals or suspected products with two methods using high-performance liquid chromatography.	2007 May 1	17196448
Simultaneous quantification of 9-(beta-D-1,3-dioxolan-4-yl)guanine, Amdoxovir and Zidovudine in human plasma by liquid chromatography-tandem mass spectrometric assay.	2009 Nov 1	19740712
Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals.	2010	20386073
Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.	2010 Apr 1	20376347
Simultaneous quantification of intracellular natural and antiretroviral nucleosides and nucleotides by liquid chromatography-tandem mass spectrometry.	2010 Mar 1	20143781

Patents

Sample Use Guides

In Vivo Use Guide

300 mg twice daily

Route of Administration: Oral

In Vitro Use Guide

Amdoxovir proved equipotent at inhibiting HBV replication in HepG2 2.2.15, HepAD79 and HepAD38 cells with EC50 13, 16 and 14 ug/ml respectively.

Name

Type

Language

AMDOXOVIR

Official Name

English

(-)-DAPD

Common Name

English

amdoxovir [INN]

Common Name

English

DAPD

Code

English

AMDOXOVIR [USAN]

Common Name

English

1,3-DIOXOLANE-2-METHANOL, 4-(2,6-DIAMINO-9H-PURIN-9-YL)-, (2R,4R)-

Systematic Name

English

(2R,4R)-4-(2,6-Diamino-9H-purin-9-yl)-1,3-dioxolane-2-methanol

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C97452