Page last updated: 2024-10-15

idx184

Description

IDX184: prodrug to enhance formation in the liver of the active triphosphate of 2'-methylguanosine, a potent and specific polymerase inhibitor of the hepatitis C virus; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID135565589
CHEMBL ID3793161
SCHEMBL ID3132403
MeSH IDM0557248

Synonyms (17)

Synonym
idx184
idx-184
1036915-08-8
SCHEMBL3132403
guanosine, 2'-c-methyl-, 5'-(2-((3-hydroxy-2,2-dimethyl-1-oxopropyl)thio)ethyl n-(phenylmethyl)phosphoramidate)
unii-4w44b4s9oc
4w44b4s9oc ,
CHEMBL3793161
s-[2-[[(2r,3r,4r,5r)-5-(2-amino-6-oxo-1h-purin-9-yl)-3,4-dihydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-(benzylamino)phosphoryl]oxyethyl] 3-hydroxy-2,2-dimethyl-propanethioate
CS-0015652
s-[2-[[(2r,3r,4r,5r)-5-(2-amino-6-oxo-1h-purin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(benzylamino)phosphoryl]oxyethyl] 3-hydroxy-2,2-dimethylpropanethioate
Q27260574
HY-19558
A920559
5'-o-[(benzylamino)[2-(3-hydroxy-2,2-dimethylpropionylsulfanyl)ethoxy]phosphoryl]-2'-c-methylguanosine
DTXSID901028050
AKOS040748561

Research Excerpts

Overview

IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate. Developed to treat patients infected with hepatitis C virus.

ExcerptReference
"IDX184 is a liver-targeted nucleotide prodrug that selectively inhibits HCV NS5B polymerase."( IDX184 in combination with pegylated interferon-α2a and ribavirin for 2 weeks in treatment-naive patients with chronic hepatitis C.
Box, T; Chen, J; Dejesus, E; Dubuc-Patrick, G; Godofsky, E; Kwo, P; Lalezari, J; Lawrence, S; Mayers, D; McCarville, J; Mehra, P; Nguyen, T; O'Riordan, W; Pietropaolo, K; Poordad, F; Sullivan-Bólyai, J; Zhou, XJ, 2013
)
"IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. "( Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.
Bhadresa, S; Bu, C; Cohen, ML; Gasparac, R; Good, SS; Gupta, K; Mayes, BA; Moussa, A; Pan-Zhou, XR; Rashidzadeh, H; Rush, R; Smith, S, 2016
)
"IDX184 is a nucleotide prodrug designed to enhance formation in the liver of the active triphosphate of 2'-methylguanosine (2'-MeG), a potent and specific polymerase inhibitor of the hepatitis C virus (HCV). "( Safety and pharmacokinetics of IDX184, a liver-targeted nucleotide polymerase inhibitor of hepatitis C virus, in healthy subjects.
Chen, J; Khan, S; Mayers, D; Pietropaolo, K; Sullivan-Bólyai, J; Zhou, XJ, 2011
)
"IDX184 is a liver-targeted prodrug of 2'-methylguanosine (2'-MeG) monophosphate. "( Short-term monotherapy with IDX184, a liver-targeted nucleotide polymerase inhibitor, in patients with chronic hepatitis C virus infection.
Asmuth, D; Casiró, A; Chen, J; Dubuc-Patrick, G; Lalezari, J; Lawrence, S; Mayers, D; McCarville, J; Pietropaolo, K; Sullivan-Bólyai, J; Vargas, H; Zhou, XJ, 2012
)

Toxicity

ExcerptReference
" IDX184 was safe and well tolerated; no serious adverse events (SAEs), dose-dependent adverse events (AEs), or dose-limiting toxicities were observed."( Safety and pharmacokinetics of IDX184, a liver-targeted nucleotide polymerase inhibitor of hepatitis C virus, in healthy subjects.
Chen, J; Khan, S; Mayers, D; Pietropaolo, K; Sullivan-Bólyai, J; Zhou, XJ, 2011
)

Pharmacokinetics

ExcerptReference
" Plasma and urine pharmacokinetic sampling was performed over a period of 120 h after dosing."( Safety and pharmacokinetics of IDX184, a liver-targeted nucleotide polymerase inhibitor of hepatitis C virus, in healthy subjects.
Chen, J; Khan, S; Mayers, D; Pietropaolo, K; Sullivan-Bólyai, J; Zhou, XJ, 2011
)
" A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction."( Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.
Bhadresa, S; Bu, C; Cohen, ML; Gasparac, R; Good, SS; Gupta, K; Mayes, BA; Moussa, A; Pan-Zhou, XR; Rashidzadeh, H; Rush, R; Smith, S, 2016
)

Compound-Compound Interactions

IDX184 in combination with P/R for 14 days was well tolerated and demonstrated greater antiviral activity. More patients achieving undetectable viral load than P-R.

ExcerptReference
" Sequential cohorts of 20 patients, randomized 16:4 (active:placebo), received IDX184 for 14 days at rising daily doses of 50, 100, 150 or 200 mg in combination with P/R for 14 days."( IDX184 in combination with pegylated interferon-α2a and ribavirin for 2 weeks in treatment-naive patients with chronic hepatitis C.
Box, T; Chen, J; Dejesus, E; Dubuc-Patrick, G; Godofsky, E; Kwo, P; Lalezari, J; Lawrence, S; Mayers, D; McCarville, J; Mehra, P; Nguyen, T; O'Riordan, W; Pietropaolo, K; Poordad, F; Sullivan-Bólyai, J; Zhou, XJ, 2013
)
"IDX184 in combination with P/R for 14 days was well tolerated and demonstrated greater antiviral activity with more patients achieving undetectable viral load than P/R."( IDX184 in combination with pegylated interferon-α2a and ribavirin for 2 weeks in treatment-naive patients with chronic hepatitis C.
Box, T; Chen, J; Dejesus, E; Dubuc-Patrick, G; Godofsky, E; Kwo, P; Lalezari, J; Lawrence, S; Mayers, D; McCarville, J; Mehra, P; Nguyen, T; O'Riordan, W; Pietropaolo, K; Poordad, F; Sullivan-Bólyai, J; Zhou, XJ, 2013
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID1293404Cytotoxicity against African green monkey Vero cells after 3 days by hemocytometry2016ACS medicinal chemistry letters, Jan-14, Volume: 7, Issue:1
Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication.
AID1463884Dose normalized AUC (0 to 24 hrs) in mouse plasma assessed as 2'-C-MeU level at 10 mg/kg, po administered as single dose2017Bioorganic & medicinal chemistry letters, 09-15, Volume: 27, Issue:18
The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.
AID1293401Antiviral activity against HCV infected in HuH7 Clone B cells assessed as inhibition of viral replication after 5 days by RT-PCR method2016ACS medicinal chemistry letters, Jan-14, Volume: 7, Issue:1
Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication.
AID1293402Cytotoxicity against human PBMC after 6 days by trypan blue exclusion assay2016ACS medicinal chemistry letters, Jan-14, Volume: 7, Issue:1
Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication.
AID1293403Cytotoxicity against human CEM cells after 6 days by trypan blue exclusion assay2016ACS medicinal chemistry letters, Jan-14, Volume: 7, Issue:1
Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication.
AID1463885Dose normalized AUC (0 to 24 hrs) in mouse liver assessed as 2'-C-MeUTP level at 10 mg/kg, po administered as single dose2017Bioorganic & medicinal chemistry letters, 09-15, Volume: 27, Issue:18
The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.
AID1463866Antiviral activity against HCV genotype 1b Con1 expressing NS3 protease infected in human Huh-7 cells assessed as reduction in viral RNA replication after 72 hrs by luciferase reporter gene assay2017Bioorganic & medicinal chemistry letters, 09-15, Volume: 27, Issue:18
The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.
AID1293405Cytotoxicity against human HuH7 cells infected with HCV assessed as reduction in cellular rRNA level after 96 hrs by qRT-PCR analysis2016ACS medicinal chemistry letters, Jan-14, Volume: 7, Issue:1
Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication.
AID1463883Selectivity index, ratio of CC50 for human Huh-7 cells to EC50 for HCV genotype 1b Con1 expressing NS3 protease2017Bioorganic & medicinal chemistry letters, 09-15, Volume: 27, Issue:18
The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (13)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's12 (92.31)24.3611
2020's1 (7.69)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4 (30.77%)5.53%
Reviews1 (7.69%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other8 (61.54%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]