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 Source | ID |
|---|---|
| PubMed CID | 135565589 |
| CHEMBL ID | 3793161 |
| SCHEMBL ID | 3132403 |
| MeSH ID | M0557248 |
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.
Toxicity
| Excerpt | Reference |
|---|---|
| " 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
| Excerpt | Reference |
|---|---|
| " 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.
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Bioassays (9)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1293404 | Cytotoxicity against African green monkey Vero cells after 3 days by hemocytometry | 2016 | ACS 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. |
| AID1463884 | Dose normalized AUC (0 to 24 hrs) in mouse plasma assessed as 2'-C-MeU level at 10 mg/kg, po administered as single dose | 2017 | Bioorganic & 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. |
| AID1293401 | Antiviral activity against HCV infected in HuH7 Clone B cells assessed as inhibition of viral replication after 5 days by RT-PCR method | 2016 | ACS 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. |
| AID1293402 | Cytotoxicity against human PBMC after 6 days by trypan blue exclusion assay | 2016 | ACS 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. |
| AID1293403 | Cytotoxicity against human CEM cells after 6 days by trypan blue exclusion assay | 2016 | ACS 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. |
| AID1463885 | Dose normalized AUC (0 to 24 hrs) in mouse liver assessed as 2'-C-MeUTP level at 10 mg/kg, po administered as single dose | 2017 | Bioorganic & 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. |
| AID1463866 | Antiviral 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 assay | 2017 | Bioorganic & 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. |
| AID1293405 | Cytotoxicity against human HuH7 cells infected with HCV assessed as reduction in cellular rRNA level after 96 hrs by qRT-PCR analysis | 2016 | ACS 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. |
| AID1463883 | Selectivity index, ratio of CC50 for human Huh-7 cells to EC50 for HCV genotype 1b Con1 expressing NS3 protease | 2017 | Bioorganic & 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)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 12 (92.31) | 24.3611 |
| 2020's | 1 (7.69) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 4 (30.77%) | 5.53% |
| Reviews | 1 (7.69%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 8 (61.54%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||