Delving into the Latest Updates on Brecanavir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Brecanavir (USAN), GW 0385, GW 640385

+ [6]

Target

HIV-1 protease

Mechanism

HIV-1 protease inhibitors(HIV protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

HIV Infections

Originator Organization

Vertex Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

ViiV Healthcare Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC33H41N3O10S2

InChIKeyJORVRJNILJXMMG-OLNQLETPSA-N

CAS Registry313682-08-5

Phase IIB, Randomized, Multicenter, Parallel Group, Study to Evaluate the Safety, Pharmacokinetics and Antiviral Effect of Four Blinded Dosing Regimens of GW640385X/Ritonavir Compared to Open-label Current PI Therapy in HIV-1 Infected, Protease Inhibitor Experienced Adults for 2 Weeks With Long-term Assessment (>48 Weeks) of Safety, Pharmacokinetic and Antiviral Activity of Selected 385/RTV Dosing Regimen(s) vs. a Ritonavir-boosted, Protease Inhibitor Containing Regimen

This is a two phase study (randomised and non-randomised phase). The randomised phase will initially examine 4 blinded doses of GW640385 boosted with rtv (with continuation of current background therapy) in comparison to an ongoing, open-labeled rtv-boosted protease inhibitor (PI) regimen for 15 days. At the Day 15 visit, all subjects will optimize background therapy. Additionally, subjects receiving the lowest dose of GW640385 will be re-randomised to one of the higher doses and subjects in the control arm will receive a new rtv-boosted PI based on resistance testing at screening. Subjects will remain in the randomized phase on one of these 4 continuing treatment arms for at least 48 weeks. An interim analysis will occur during the randomised phase to select for a dose of GW640385 to evaluate further in Phase III studies. After dose selection subjects will move to the non-randomised phase of the study. In the non-randomised phase subjects who are receiving GW640385 will be assigned to final selected dose for assessment of long term safety, tolerability, pharmacokinetics, and antiviral activity.

Start Date01 Aug 2005

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT00257621

/ CompletedPhase 2

A Pilot, Phase II, Open-label, Single Arm Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of GW640385 When Administered With Ritonavir in Combination With NRTIs for 48 Weeks in HIV-1 Infected Adults

This is a proof of concept (POC) single arm study of GW640385, a protease inhibitor, in combination with RTV and 2 or more nucleoside reverse transcriptase inhibitors (NRTI) backbone. This study has a 48 week duration and is open to both treatment naive and experienced patients who are HIV positive. There are 3 intensive pharmacokinetic (PK) visits.

Start Date01 Oct 2004

Sponsor / Collaborator

ViiV Healthcare Ltd.

100 Clinical Results associated with Brecanavir

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100 Translational Medicine associated with Brecanavir

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100 Patents (Medical) associated with Brecanavir

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40

Literatures (Medical) associated with Brecanavir

24 Mar 2022·Journal of biomolecular structure & dynamics

Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study

Article

Author: Emirik, Mustafa

Inspired by the 'There is no scientific evidence that turmeric prevents COVID-19' statement made by WHO, the protective or therapeutic potential of the compounds in turmeric contents was investigated against COVID-19 with in silico methodology. The drugs used for experimental COVID-19 therapies were included in this study using the same method for comparison with turmeric components. The 30 turmeric compounds and nine drugs were performed in the docking procedure for vital proteins of COVID-19. With evaluations based on docking scores, the Prime MMGBSA binding free energy and protein-ligand interactions were identified in detail. The 100 ns MD simulations were also performed to assess the stability of the ligands at the binding site of the target proteins. The Root Mean Square Deviation (RMSD) is used to obtain the average displacement for a particular frame concerning a reference frame. The results of this study are suggesting that turmeric spice have a potential to inhibit the SARS-CoV-2 vital proteins and can be use a therapeutic or protective agent against SARS-CoV-2 via inhibiting key protein of the SARS-CoV-2 virus. The compound 4, 23 and 6 are the most prominent inhibitor for the main protease, the spike glycoprotein and RNA polymerase of virus, respectively. The MD simulation validated the stability of ligand-protein interactions. The compactness of the complexes was shown using a radius of gyration. ADME properties of featured compounds are in range of 95% drug molecules. It is hoped that the outputs of this study will contribute to the struggle of humanity with COVID-19.Communicated by Ramaswamy H. Sarma.

21 Jun 2021·Chemical research in toxicologyQ3 · MEDICINE

Reactive Metabolites from Thiazole-Containing Drugs: Quantum Chemical Insights into Biotransformation and Toxicity

Q3 · MEDICINE

Article

Author: Jaladanki, Chaitanya K. ; Khatun, Samima ; Gohlke, Holger ; Bharatam, Prasad V.

Drugs containing thiazole and aminothiazole groups are known to generate reactive metabolites (RMs) catalyzed by cytochrome P450s (CYPs). These RMs can covalently modify essential cellular macromolecules and lead to toxicity and induce idiosyncratic adverse drug reactions. Molecular docking and quantum chemical hybrid DFT study were carried out to explore the molecular mechanisms involved in the biotransformation of thiazole (TZ) and aminothiazole (ATZ) groups leading to RM epoxide, S-oxide, N-oxide, and oxaziridine. The energy barrier required for the epoxidation is 13.63 kcal/mol, that is lower than that of S-oxidation, N-oxidation, and oxaziridine formation (14.56, 17.90, and 20.20, kcal/mol respectively). The presence of the amino group in ATZ further facilitates all the metabolic pathways, for example, the barrier for the epoxidation reaction is reduced by ∼2.5 kcal/mol. Some of the RMs/their isomers are highly electrophilic and tend to form covalent bonds with nucleophilic amino acids, finally leading to the formation of metabolic intermediate complexes (MICs). The energy profiles of these competitive pathways have also been explored.

15 Jul 2020·Journal of computational chemistryQ3 · CHEMISTRY

Accurate prediction of relative binding affinities of a series of HIV‐1 protease inhibitors using semi‐empirical quantum mechanical charge

Q3 · CHEMISTRY

Article

Author: Zhu, Weiliang ; Xu, Zhijian ; Peng, Cheng ; Cai, Tingting ; Wang, Jinan

Abstract:

A major challenge in computer‐aided drug design is the accurate estimation of ligand binding affinity. Here, a new approach that combines the adaptive steered molecular dynamics (ASMD) and partial atomic charges calculated by semi‐empirical quantum mechanics (SQMPC), namely ASMD‐SQMPC, is suggested to predict the ligand binding affinities, with 24 HIV‐1 protease inhibitors as testing examples. In the ASMD‐SQMPC, the relative binding free energy (ΔG) is reflected by the average maximum potential of mean force (max) between bound and unbound states. The correlation coefficient (R2) between the max and experimentally determined ΔG is 0.86, showing a significant improvement compared with the conventional ASMD (R2 = 0.52). Therefore, this study provides an efficient approach to predict the relative ΔG and reveals the significance of precise partial atomic charges in the theoretical simulations.

100 Deals associated with Brecanavir

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