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

Action

inhibitors

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.

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (China)

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Structure/Sequence

Molecular FormulaC36H46ClN5O5S

InChIKeyIHXVACFNNPBRLK-VTFHPOPBSA-N

CAS Registry958002-36-3

View All Structures (2)

The most common cause of respiratory tract illness in newborns and young children is the respiratory syncytial virus (RSV). There is no approved vaccination or specific antiviral medication for RSV infections. Here, an attempt has been made to explore the potential of currently marketed drugs as well as their probable derivatives to improve the possibility of developing stronger medications against RSV. From the 100 synthetic drug compounds library, the best drug molecule was identified through drug-likeness properties, toxicity, molecular docking and molecular dynamics simulations. Molecular Mechanics Generalized Born Surface Area (MM-GBSA) was also a method that was applied in this study. Daclatasvir showed the highest binding energy and appeared as the best drug to inhibit matrix protein and a fusion protein of RSV. Based on Daclatasvir, 40 computational derivatives were made. D28, D34 and D40 showed far better results than the actual drug. Changes in lipophilicity character increase the binding energy of derivatives. Molecular dynamic simulations showed their non-deviated, non-fluctuated and stable complex formation with target proteins. The high number of amino acid contacts throughout the trajectory increases the stability and effectiveness of derivatives. The key to producing a novel medicine to eradicate RSV is provided by derivatives. Daclatasvir will be employed as a potential RSV inhibitor up until that point.

18 Sep 2024·ChemistrySelect

Computational Screening of FDA‐Approved Hepatitis C Drugs for Inhibition of VEGFR2 in Liver Cancer

Author: Aluwi, Mohd Fadhlizil Fasihi Mohd ; Tufail, Nasir ; Wilhelm, Anke ; Issahaku, Abdul Rashid ; Roney, Miah

AbstractLiver cancer (LC) is one of the most common tumours and the leading cause of cancer‐related death globally. Amidst the problems associated with existing treatments, such as hepatotoxicity, recurrence, drug resistance, and other adverse effects, researchers are under pressure to find alternatives. Towards a comprehensive rationalisation of the search for new anti‐LC drugs among approved ones, we employed an in‐silico approach to accelerate the selection of the most efficacious LC drugs. The FDA‐approved hepatitis C virus (HCV) drugs were docked with the LC protein using the AutoDock Vina software. Compared to the control compound, two FDA‐approved HCV drugs (DB09102 and DB09027) were selected based on their binding energies and interactions with the target protein, which showed comparable binding energies. Furthermore, these compounds were then subjected to molecular dynamic simulation, principle component analysis, and MMGBSA using the AMBER20 software, and the results showed stable complexes compared to the control complex. All things considered, this study will help the scientific community and society find a novel drug to treat LC.

01 Aug 2024·Regulatory Toxicology and Pharmacology

Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals

Article

Author: Nimrod Perkins, Alison ; Lee, Michael R ; Janer, Gemma ; Häner, Andreas ; Ryan, James J ; Nfon, Erick ; Burden, Natalie ; Maynard, Samuel K ; Dolan, David G ; Constantine, Lisa A ; Tell, Joan ; Davidson, Todd

In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified.

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	United States	Bristol Myers Squibb Co.	01 Feb 2014
Chronic hepatitis C genotype 1	Phase 3	Australia	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 3	Canada	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 3	United States	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 3	France	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	United States	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	France	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	Canada	Bristol Myers Squibb Co.	01 Dec 2013
Fibrosis	Phase 3	Australia	Bristol Myers Squibb Co.	01 Dec 2013
Hepatitis C, Chronic	Phase 3	Puerto Rico	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


NCT02124044 (CTgov)	Phase 2	Hepatitis C	30	Asunaprevir+Daclatasvir+BMS-791325 (HIV/HCV GT-1a/1b, 12 Wks ASV/DCV With BMS-791325)	ymxwrklyty(xrrbgkftcr) = zsedwhqooz qymxocczen (yvbkfiemnd, audphroxmy - rtcqltjwcc) View more	-	13 Apr 2017
				Asunaprevir+Daclatasvir (HIV/HCV GT-1b, 24 Wks ASV/DCV)	ymxwrklyty(xrrbgkftcr) = wsrgxfzyon qymxocczen (yvbkfiemnd, nvhxebcoyq - myuyzogxop) View more
NCT01973049 (UNITY-2, Pubmed \| JAMA)	Phase 3	Hepatitis C \| Compensated cirrhosis	202	Daclatasvir + Asunaprevir + Beclabuvir + Ribavirin	dxbsrmsmau(nixkzzyupf) = Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation rgmskmmkfl (wvidqhdrpw ) View more	-	05 May 2015
				Daclatasvir + Asunaprevir + Beclabuvir
NCT01455090 (Pubmed \| Gastroenterology)	Phase 2	Hepatitis C	66	Daclatasvir	(mxafwqbghk) = qqvvbmrpmb fxsqxdbqgd (jqqhlgcmrr )	-	01 Feb 2014
				Asunaprevir	(mxafwqbghk) = kfepnnfcyb fxsqxdbqgd (jqqhlgcmrr )