Delving into the Latest Updates on Beclabuvir hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Beclabuvir, Beclabuvir hydrochloride (JAN/USAN)

+ [1]

Target

NS5B polymerase

Mechanism

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

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases+ [1]

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1FibrosisHepatitis C+ [2]

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

Bristol Myers Squibb Co.

Bristol-Myers Squibb (China) Investment Co. Ltd.Bristol-Myers Squibb Pharmaceuticals Ltd.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC36H46ClN5O5S

InChIKeyIHXVACFNNPBRLK-VTFHPOPBSA-N

CAS Registry958002-36-3

View All Structures (2)

Abstract:Asunaprevir, daclatasvir, and beclabuvir are direct-acting antiviral agents used in the treatment of patients infected with hepatitis C genotype 1b. This article reviews the biotransformation and disposition of these drugs in relation to the safety and efficacy of therapy. CYP3A4 and 3A5 catalyze the oxidative biotransformation of the drugs, while P-glycoprotein mediates their efflux from tissues. Asunaprevir is also a substrate for the influx transporters OATP1B1 and OATP2B1 and the efflux transporter MRP2, while beclabuvir is also a substrate for the efflux transporter BCRP. Liver disease decreases the expression of CYPs and transporters that mediate drug metabolism and disposition. Serum asunaprevir concentrations, but not those of daclatasvir or beclabuvir, are increased in patients with severe liver disease, which may produce toxicity. Pharmacogenomic variation in CYPs and transporters also has the potential to disrupt therapy with asunaprevir, daclatasvir and beclabuvir; some variants are more prevalent in certain racial groups. Pharmacokinetic drug-drug interactions, especially where asunaprevir, daclatasvir, and beclabuvir are victim drugs, are mediated by coadministered rifampicin, ketoconazole and ritonavir, and are attributable to inhibition and/or induction of CYPs and transporters. Conversely, there is also evidence that asunaprevir, daclatasvir and beclabuvir are perpetrators of drug interactions with coadministered rosuvastatin and dextromethorphan. Together, liver disease, pharmacogenomic variation and drug-drug interactions may disrupt therapy with asunaprevir, daclatasvir and beclabuvir due to the impaired function of important CYPs and transporters.

21 Dec 2023·Journal of Biomolecular Structure and Dynamics

Novel pseudonucleosides and sulfamoyl-oxazolidinone β - D -glucosamine derivative as anti-COVID-19: design, synthesis, and in silico study

Article

Author: Zerrouki, Rachida ; Bouzina, Abdeslem ; Aouf, Zineb ; Aouf, Nour Eddine ; Ibrahim-Ouali, Malika ; Sekiou, Omar ; Mansouri, Rachida

New pseudonucleosides containing cyclic sulfamide moiety and sulfamoyl β-D-glucosamine derivative are described. These pseudonucleosides are synthesized in good yields starting from chlorosulfonyl isocyanate and β-D-glucosamine hydrochloride in five steps; (protection, acetylation, removal of the Boc group, sulfamoylation, and cyclization). Further, novel glycosylated sulfamoyloxazolidin-2-one is prepared in three steps; carbamoylation, sulfamoylation, and intramolecular cyclization. The structures of the synthesized compounds were confirmed by usual spectroscopic and spectrometric methods NMR, IR, MS, and EA. Interesting molecular docking of the prepared pseudonucleosides and (Beclabuvir, Remdesivir) drugs with SARS-CoV-2/M^pro (PDB:5R80) was conducted using the same parameters for a fair comparison. A low binding affinity of the synthesized compounds compared to the Beclabuvir and other analysis showed that pseudonucleosides have the ability to inhibit SARS-CoV-2. After the motivating results of molecular docking study, the complex between the SARS-CoV-2 M^pro and compound 7 was subjected to 100 ns molecular dynamics (MD) simulation using Desmond module of Schrodinger suite, during which the receptor-ligand complex showed substantial stability after 10 ns of MD simulation. Also, we studied the prediction of absorption, distribution, properties of metabolism, excretion, and toxicity (ADMET) of the synthesized compounds.Communicated by Ramaswamy H. Sarma.

01 Feb 2022·Journal of Molecular StructureQ3 · CHEMISTRY

Re-purposing of hepatitis C virus FDA approved direct acting antivirals as potential SARS-CoV-2 protease inhibitors

Q3 · CHEMISTRY

Article

Author: Uddin, Reaz ; Ul-Haq, Zaheer ; Jalal, Khurshid ; Khan, Kanwal

A new coronavirus strain called as SARS-CoV-2 has emerged from Wuhan, China in late 2019 and it caused a worldwide pandemic in a few months. After the Second World War, it is the biggest calamity observed as there is no specific US Food and Drugs Administration (USFDA) approved drug or vaccine available globally for the treatment. Several clinical trials are ongoing for therapeutic alternatives, however with little success rate. Considering that the time is crucial, the drug repurposing and data obtained from in silico models are one of the most important approaches to identify possible lead inhibitors against SARS-CoV-2. More recently, the Direct Acting Antivirals (DAAs) are emerged as the most promising drugs to control viral infection. The Main Protease (Mpro), a key enzyme in the SARS-CoV-2 replication cycle, is found close homolog to the Hepatitis C Virus (HCV) protease and could be susceptible of blocking its activity by DAAs. In the current study, the DAAs were investigated as antivirals using structure based computational approach against Mpro of SARS-CoV-2 to propose them as new therapeutics. In total, 20 DAAs of HCV, including a reference compound O6K were docked against Mpro. The docked structures were examined and resulted in the identification of six highly promising DAAs i.e. beclabuvir, elbasvir, paritaprevir, grazoprevir, simeprevir, and asunapevir exhibiting high theoretical binding affinity to Mpro from SARS-CoV-2 in comparison to other DAAs. Furthermore, the post docking analysis revealed that Cys145, Glu166, His163, Thr26, His41, and Met165 played potential role for the binding of these DAAs inside binding site of Mpro. Furthermore, the correlation between binding energies were found in accord with the results from the reported IC₅₀s for some DAAs. Overall, the current study provides insight to combat COVID-19 using FDA-approved DAAs as repurposed drugs.

100 Deals associated with Beclabuvir hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D10611	Beclabuvir hydrochloride	-	DB12225

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 3	GB	Bristol Myers Squibb Co.	01 Apr 2014
Chronic hepatitis C genotype 1	Phase 3	US	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 3	FR	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 3	AU	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 3	CA	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	US	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	AU	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	CA	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	FR	Bristol Myers Squibb Co.	01 Dec 2013
Hepatitis C, Chronic	Phase 3	PR	Bristol Myers Squibb Co.	30 Nov 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01973049 (UNITY-2, Pubmed \| J Coll Physicians Surg Pak)	Phase 3	Hepatitis C \| Compensated cirrhosis	202	Daclatasvir + Asunaprevir + Beclabuvir + Ribavirin	kfstolzsef(xqgegnnrtv) = Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation idhyogtzjv (wmixjoviyr ) View more	-	05 May 2015
				Daclatasvir + Asunaprevir + Beclabuvir
NCT01455090 (Pubmed \| J Laparoendosc Adv Surg Tech A)	Phase 2	Chronic hepatitis C genotype 1	66	Daclatasvir	(xtbzysziuf) = bdwyrprxco iqduxqjssr (zverufkqgn )	-	01 Feb 2014
				Asunaprevir	(xtbzysziuf) = mrdzkrnahz iqduxqjssr (zverufkqgn )