ZIDOVUDINE MONOPHOSPHATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H14N5O7P
Molecular Weight	347.2212
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CN([C@H]2C[C@H](N=[N+]=[N-])[C@@H](COP(O)(O)=O)O2)C(=O)NC1=O

InChI

InChIKey=OIFWQOKDSPDILA-XLPZGREQSA-N

InChI=1S/C10H14N5O7P/c1-5-3-15(10(17)12-9(5)16)8-2-6(13-14-11)7(22-8)4-21-23(18,19)20/h3,6-8H,2,4H2,1H3,(H,12,16,17)(H2,18,19,20)/t6-,7+,8+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14725491 | https://www.ncbi.nlm.nih.gov/pubmed/27941394 | http://adisinsight.springer.com/drugs/800007452

Fozivudine tidoxil is a thioether lipid–Zidovudine (ZDV) conjugate. After intake it is split intracellularly into the lipid moiety and ZDV-monophosphate, which is subsequently phosphorylated to the active metabolite ZDV-triphosphate. The rationale behind the development of fozivudine (FZD) was to take advantage of the high cleavage activity in mononuclear cells and other organs resulting in increased amounts of intracellular ZDV available for phosphorylation to the active metabolite, and a very low activity in red blood and stem cells, which should result in reduced haematologic toxicity. It is member of the family of nucleoside reverse transcriptase (RT) inhibitors. Fozivudine tidoxil has been in Phase II clinical trials for the treatment of HIV infection. There were three adverse events possibly related to fozivudine: urine abnormality, gastrointestinal pain and abnormal dreams.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14725491 \| http://adisinsight.springer.com/drugs/800007452	Inhibitor 8297
pol polyprotein 2 Target ID: 1489989.0 Gene Symbol: pol Sources: https://www.ncbi.nlm.nih.gov/pubmed/21457319	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27941394 https://www.ncbi.nlm.nih.gov/pubmed/10839658	Primary		Phase II 1132	Unknown Approved Use Unknown
Feline immunodeficiency virus 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22816034	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
30.03 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZIDOVUDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
69.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZIDOVUDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
70.54 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZIDOVUDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.92 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FOZIVUDINE TIDOXIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.14 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FOZIVUDINE TIDOXIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.39 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FOZIVUDINE TIDOXIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
7.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZIDOVUDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZIDOVUDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZIDOVUDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FOZIVUDINE TIDOXIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FOZIVUDINE TIDOXIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10839658	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FOZIVUDINE TIDOXIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		P-gp 257

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/18690875/	yes	ZIDOBUDINE 2

Sourcing

Vendor/Aggregator	ID	URL
Hangzhou Yuhao Chemical Technology	RT16637
Toronto Research Chemicals	B692055	https://www.trc-canada.com/product-detail/?CatNum=B692055
eMolecules	193061341	https://orderbb.emolecules.com/search/#?query=193061341
eMolecules	225416716	https://orderbb.emolecules.com/search/#?query=225416716
eMolecules	271404373	https://orderbb.emolecules.com/search/#?query=271404373
eMolecules	300471354	https://orderbb.emolecules.com/search/#?query=300471354
eMolecules	300658342	https://orderbb.emolecules.com/search/#?query=300658342

PubMed

Title	Date	PubMed
Phase I/II trial with fozivudine tidoxil (BM 21.1290): a 7 day randomized, placebo-controlled dose-escalating trial.	1997 Dec	11327445
Single dose, dose-escalating trial with fozivudine tidoxil (BM 21.1290).	1997 Dec	11327444
Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficacy.	2000 Mar 1	10839658
Fozivudine: BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867.	2004	14725491
Mitochondrial DNA depletion in rat liver induced by fosalvudine tidoxil, a novel nucleoside reverse transcriptase inhibitor prodrug.	2009 Jul	19433557
Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.	2017 Feb 20	27941394

Patents

Sample Use Guides

In Vivo Use Guide

800 mg once daily or 600 mg twice daily or 1200 mg once daily over a period of 24 weeks.

Route of Administration: Oral

In Vitro Use Guide

Fozivudine showed dose-dependent inhibition of various HIV strains in vitro, with IC50 values of 0.02–0.2 uM/L (15–150 ng/mL).

Name

Type

Language

ZIDOVUDINE MONOPHOSPHATE

Common Name

English

AZT-MP

Common Name

English

AZIDOTHYMIDINE MONOPHOSPHATE

Systematic Name

English

3'-AZIDO-3'-DEOXYTHYMIDINE 5'-PHOSPHATE

Systematic Name

English

5'-THYMIDYLIC ACID, 3'-AZIDO-3'-DEOXY-

Common Name

English

AZT 5'-MONOPHOSPHATE

Common Name

English

Code System Code Type Description

DRUG BANK

DB03666