Delving into the Latest Updates on Radalbuvir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

GS-9669

Target

NS5B polymerase

Action

inhibitors

Mechanism

NS5B polymerase inhibitors(Hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1Hepatitis CHepatitis C, Chronic

Originator Organization

Gilead Sciences, Inc.

Active Organization-

Inactive Organization

Gilead Sciences, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC30H41NO6S

InChIKeyMUICUPWICXUNRS-GDCCIXDYSA-N

CAS Registry1314795-11-3

This study will evaluate the antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) or LDV/SOF plus GS-9669 in treatment-naive or treatment-experienced participants with chronic genotype 1 hepatitis C virus (HCV) infection. A total of 90 participants are planned to be enrolled in the study for 8 weeks of treatment, approximately 60 having had prior treatment with a regimen containing pegylated interferon (PEG) and RBV for ≥ 12 weeks. Randomization will be stratified by treatment-naive versus treatment-experienced and by HCV genotype (1a versus 1b).

Start Date01 Oct 2013

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT01826981

/ CompletedPhase 2

A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection

The purpose of this study is to evaluate the antiviral efficacy, safety, tolerability of combination therapy with sofosbuvir (SOF) containing regimens for the treatment of chronic hepatitis C virus (HCV) infection.

Start Date01 Apr 2013

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT01805882

/ CompletedPhase 2IIT

A Pilot Study to Evaluate the Safety and Efficacy of Multiple Anti-HCV Combination Therapy in Chronically Infected Hepatitis C Patients

Background:
- GS-7977, GS-5885, GS-9669, and GS-9451 are new drugs for treating hepatitis C virus (HCV) infection. GS-7977 may help treat the infection when used with other treatments like interferon therapy. GS-5885, and GS-9669, and GS-9451 also lower the amount of HCV in the body. Researchers want to see whether GS-7977 can be combined with any of the other three drugs to treat HCV infection. Some participants will take GS-7977 and GS-5885. Others will take GS-7977, GS-5885 and GS-9669 or GS-7977, GS-5885 and GS-9451.
Objectives:
- To see whether GS-7977 with GS-5885 alone or in combination with either GS-9669 or 9451 can be used to treat HCV infection.
Eligibility:
Individuals at least 18 years of age who have chronic HCV infection and have never been treated for it.
Individuals at least 18 years of age who have chronic HCV infection and have not responded to interferon therapy.
Individuals at least 18 years of age who have chronic HCV infection with advanced liver disease and have never been treated for HCV
Design:
Participants will be screened with a physical exam and medical history. Blood samples will be collected. A liver biopsy may also be performed.
Some participants will take the two study drugs and some will take three study drugs. Those who take GS-7977 and GS-5885 will have one daily tablet named fixed dose combination or FDC. Those who take GS-7977 and CS-9669 will have three daily tablets taken once daily. Those who take GS-7977 and GS-5885 and GS-9451 will take 2 pills once a day. GS-7977 and GS-5885 will be combined in one pill and GS-9451 will be in another pill.
Treatment will be monitored with frequent blood tests. These tests will check liver function and the level of HCV infection. Participants may have other blood tests as needed for treatment.
Participants will have 4, 6 or 12 weeks of treatment depending on which study drugs are scheduled to take. After they complete their schedule, they will stop treatment with the study drugs. They may also have another liver biopsy.
Participants will have regular follow-up visits over the next 48 weeks. They will have physical exams and provide blood samples....

Start Date01 Jan 2013

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with Radalbuvir

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100 Translational Medicine associated with Radalbuvir

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100 Patents (Medical) associated with Radalbuvir

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28

Literatures (Medical) associated with Radalbuvir

21 Dec 2023·Journal of biomolecular structure & dynamics

Dynamics and binding affinity of nucleoside and non-nucleoside inhibitors with RdRp of SARS-CoV-2: a molecular screening, docking, and molecular dynamics simulation study

Article

Author: Ramadurai, Prakash ; Chinnamadhu, Archana ; Suresh, Suganya ; Poomani, Kumaradhas ; Ramakrishnan, Jaganathan

In this COVID-19 pandemic situation, an appropriate drug is urgent to fight against this infectious disease to save lives and prevent mortality. Repurposed drugs and vaccines are the immediate solutions for this medical emergency until discover a new drug to treat this disease. As of now, no specific drug is available to cure this disease completely. Several drug targets were identified in SARS-CoV-2, in which RdRp protein is one of the potential targets to inhibit this virus infection. In-Silico studies plays a vital role to understand the binding nature of the drugs at the atomic level against the disease targets. The present study explores the binding mechanism of reported 53 nucleoside and non-nucleoside RdRp inhibitors and Ivermectin which are in clinical trials. These molecules were screened by molecular docking simulation; in which, the molecules are showing high binding affinity and forming interactions with the key amino acids of active site of RdRp protein are chosen for molecular dynamics simulation (MD) and binding free energy analysis. The results of molecular docking and MD simulation studies reveal that IDX184 is a stable molecule and forms strong interactions with the key amino acids and shows high binding affinity towards RdRp. Hence, IDX184 may also be considered as a potential inhibitor of RdRp after clinical study.Communicated by Ramaswamy H. Sarma.

01 May 2021·MEDICINAL CHEMISTRY RESEARCH

Synthesis, docking, and biological evaluation of thiazolidinone derivatives against hepatitis C virus genotype 4a

Author: Ahmed S. Al-Behery ; Kamel M. Elberembally ; Mohammed A. Eldawy

Hepatitis C virus (HCV) genotype 4a (GT4a) is prevalent in Egypt.It did not gain the necessary scientific focus despite its high resistance.Since the crystal structure NS5B (RNA-dependent RNA polymerase) of HCV GT4a has not been resolved until now, homol. modeling was conducted to build and validate the 3D model of the enzyme.Ligand binding sites including the allosteric thumb II pocket were detected and used in lead optimization.Sixty new 4-thiazolidinone derivatives have been virtually designed and docked into thumb II site of HCV NS5B GT4a using rigid docking approach.Eighteen compounds (7a-r) that show good docking scores were synthesized and tested in vitro against NS5B GT4a.Compounds 7b and 7n showed the best inhibitory activity (IC50 = 0.338 and 0.342μM, resp.).Compounds 7a, 7b, 7c, 7d, 7k, 7n, 7q, and 7r that have IC50 values less than 2μM were assessed for cellular anti-HCV GT4a activity using human hepatoma cell line (Huh 7.5).The percentages of viral growth inhibition are between 79.67 and 94.77%.Compound 7b is the most active in the in vitro and cellular assays and could be considered a potential new lead for future anti-HCV studies.

01 Jan 2021·Computational and structural biotechnology journalQ3 · BIOLOGY

Insight into the drug resistance mechanisms of GS-9669 caused by mutations of HCV NS5B polymerase via molecular simulation

Q3 · BIOLOGY

ArticleOA

Author: Han, Di ; Zhang, Beibei ; Wujieti, Baerlike ; Cui, Wei ; Wang, Huiqun ; Chen, Bo-Zhen

GS-9669 is a non-nucleos(t)ide inhibitor (NNI) binding to the thumb site II of the Hepatitis C virus (HCV) NS5B polymerase and has advanced into phase II trials. To clarify the drug resistance mechanisms of GS-9669 caused by M423T/I/V, L419M, R422K, and I482L mutations of NS5B polymerase (GT1b) and the receptor-ligand interactions during the binding process, a series of molecular simulation methods including molecular dynamics (MD) simulations and adaptive steered molecular dynamics (ASMD) simulations were performed for the wild-type (WT) and six mutant NS5B/GS-9669 complexes. The calculated results indicate that the binding free energies of the mutant systems are less negative than that of the WT system, indicating that these mutations will indeed cause NS5B to produce different degrees of resistance to GS-9669. The mutation-induced drug resistances are mainly caused by the loss of binding affinities of Leu419 and Trp528 with GS-9669 or the formation of multiple solvent bridges. Moreover, the ASMD calculations show that GS-9669 binds to the thumb II sites of the seven NS5B polymerases in distinct pathways without any obvious energy barriers. Although the recognition methods and binding pathways are distinct, the binding processes of GS-9669 with the WT and mutant NS5B polymerases are basically controlled thermodynamically. This study clearly reveals the resistance mechanisms of GS-9669 caused by M423T/I/V, L419M, R422K, and I482L mutations of HCV NS5B polymerase and provides some valuable clues for further optimization and design of novel NS5B inhibitors.

100 Deals associated with Radalbuvir

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Radalbuvir	-	DB12065

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic hepatitis C genotype 1	Phase 2	United States	Gilead Sciences, Inc.	01 Oct 2013
Hepatitis C	Phase 2	New Zealand	Gilead Sciences, Inc.	-
Hepatitis C, Chronic	Phase 1	Puerto Rico	Gilead Sciences, Inc.	01 Sep 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01805882 (CTgov)	Phase 2	Hepatitis C, Chronic	229	Sofosbuvir+Ledipasvir (D Retx: HCV GT-1, Re-Treatment, 12 Wks Sofosbuvir, Ledipasvir)	gudwgwrkxd = lbdvzbkuaf jaqjpflxid (fotwswdxye, owdrweuvvu - aubpabexlt) View more	-	11 Apr 2017
NCT01805882 (CTgov)	Phase 2	Hepatitis C, Chronic	229	Sofosbuvir+Ledipasvir (D: HCV GT-1, Tx-relapsed, 12 Wks Sofosbuvir/Ledipasvir)	gudwgwrkxd = yclibvoaak jaqjpflxid (fotwswdxye, cbakmyokmj - aeyyknbabu) View more	-	11 Apr 2017
NCT01984294 (CTgov)	Phase 2	Chronic hepatitis C genotype 1	101	LDV/SOF+RBV	cvvovpkkfv = zksidzskva qspcrxnrvt (bzwuuoqwdl, rlfxhxmpdg - qpzscwllez) View more	-	21 May 2015