Delving into the Latest Updates on Deleobuvir Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Deleobuvir, Deleobuvir sodium (JAN/USAN)

+ [5]

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 1Chronic hepatitis C genotype 1bHepatitis C+ [1]

Originator Organization

C.H. Boehringer Sohn AG & Co. KG

Active Organization-

Inactive Organization

Boehringer Ingelheim GmbHBoehringer Ingelheim Pharma GmbH & Co., KGBoehringer Ingelheim International GmbH

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (China)

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Structure/Sequence

Molecular FormulaC34H33BrN6O3

InChIKeyBMAIGAHXAJEULY-UKTHLTGXSA-N

CAS Registry863884-77-9

View All Structures (2)

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.

02 Jan 2022·Journal of Biomolecular Structure and Dynamics

Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2

Article

Author: Sharma, Prem Prakash ; Rathi, Brijesh ; Choudhari, Ramesh ; Kumar, Dhruv ; Raj, Sibi ; Chandel, Vaishali

Drug re-purposing might be a fast and efficient way of drug development against the novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We applied a bioinformatics approach using molecular dynamics and docking to identify FDA-approved drugs that can be re-purposed to potentially inhibit the non-structural protein 9 (Nsp9) replicase and spike proteins in SARS-CoV-2. We performed virtual screening of FDA-approved compounds, including antiviral, anti-malarial, anti-parasitic, anti-fungal, anti-tuberculosis, and active phytochemicals against the Nsp9 replicase and spike proteins. Selected hit compounds were identified based on their highest binding energy and favorable absorption, distribution, metabolism and excretion (ADME) profile. Conivaptan, an arginine vasopressin antagonist drug exhibited the highest binding energy (-8.4 Kcal/mol) and maximum stability with the amino acid residues present at the active site of the Nsp9 replicase. Tegobuvir, a non-nucleoside inhibitor of the hepatitis C virus, also exhibited maximum stability along with the highest binding energy (-8.1 Kcal/mol) at the active site of the spike proteins. Molecular docking scores were further validated by molecular dynamics using Schrodinger, which supported the strong stability of ligands with the proteins at their active sites through water bridges, hydrophobic interactions, and H-bonding. Our findings suggest Conivaptan and Tegobuvir as potential therapeutic agents against SARS-CoV-2. Further in vitro and in vivo validation and evaluation are warranted to establish how these drug compounds target the Nsp9 replicase and spike proteins.

01 Nov 2020·Arabian Journal of Chemistry

Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study

Author: Nawaf Alsaif ; Mohamed Attwa ; Maha Abou-El-Alamin ; Mostafa Mohammed ; Abdullah Al-Hossaini ; Sherif Hammad ; Mohamed Hefnawy ; Adnan Kadi ; Yousef Bin Jardan

HCV-genotype-4 (HCV-GT4) is the cause of approx. 20% of the 170 million cases of chronic hepatitis C virus (HCV) in the world.Around 95% of patients with chronic HCV infection can be cure by utilizing direct-acting antiviral treatment.Two anti-HCV genotype 4 co-administered ravidasvir (RAV) and sofosbuvir (SOF) were simultaneously quantified in rat plasma by a validated and sensitive LC-MS/MS method using aciclovir as an internal standardChromatog. resolution for all analytes was performed with an Eclipse plus C18 column (50 mm x 2.1 mm, 1.8μm) with isocratic mobile phase consisted of 10 mM ammonium formate: acetonitrile (61:39, volume/volume, pH 4.0) at a flow rate of 0.25 mL/min.Sample pre-treatment involved protein precipitation in plasma and stable internal standard resulted in a sensitive and robust method.Pos. multiple reaction monitoring (MRM) mode was chosen to identify RAV, SOF, and IS.The developed assay was validated for accuracy, precision, linearity, selectivity, extraction recovery, matrix effect, carry-over, dilution integrity, and stability in accordance with US-FDA bioanal. method validation guidelines.The method was linear over the ranges of 0.5-600 and 1-3000 ng/mL of RAV and SOF, resp. (r2 ≥ 0.997).After injection of the HLOQ sample, carry-over in the blank sample was less than 20% of the LLOQ of RAV, SOF and less than 5% of the IS.The mean relative standard deviation (RSD) of the results of accuracy and precision were ≤9.74%, and the overall recoveries of RAV and SOF from rat plasma were in the range 92.53-107.25%.The current methodol. is the first LC-MS/MS for the quantification of RAV and SOF in rat plasma and to applied the pharmacokinetics of these agents in rats.

100 Deals associated with Deleobuvir Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D10622	Deleobuvir Sodium	-	DB14850

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 3	Italy	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	Belgium	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	Portugal	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	Germany	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	New Zealand	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	France	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	Greece	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	United States	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	Canada	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	United Kingdom	Boehringer Ingelheim GmbH	01 Nov 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01830127 (HCVerso3, Pubmed \| J Biol Chem \| PLoS One) Manual	Phase 2	Fibrosis \| Hepatitis C	35	Faldaprevir+Deleobuvir+Ribavirin (moderate hepatic impairment（Child-Pugh B [CPB]）)	(pcszztwiov) = pcuqipyqjd wnmueylmjt (ipflidumne, 29.2 - 76.7) View more	Positive	28 Dec 2016
				Faldaprevir+Deleobuvir+Ribavirin (mild hepatic impairment（Child-Pugh A [CPA]）)	(pcszztwiov) = krdsrthnmg wnmueylmjt (ipflidumne, 38.6 - 83.6) View more
NCT01132313 (SOUND-C3, Pubmed \| Eur J Gastroenterol Hepatol) Manual	Phase 2	Hepatitis C	51	ribavirin+deleobuvir (receive faldaprevir 120 mg once daily with deleobuvir at either 800 mg twice daily)	(ochazlbjyl) = drnuimauok jxdxocobgm (ucykbstcye ) View more	Positive	01 Aug 2016
				ribavirin+deleobuvir (600 mg three times daily)	(ochazlbjyl) = knpusmgdyw jxdxocobgm (ucykbstcye ) View more
NCT01525628 (CTgov)	Phase 1	Chronic hepatitis C genotype 1	72	pegylated interferon+BI 207127+BI 201335+tolbutamide+midazolam+caffeine+ribavirin (Group A)	qnucjyjxkp(rweebvhzmp) = udowwdyrju tfzuokcfpu (lsxufqxdrz, idmxjikthg - qdfflenydn) View more	-	10 Jun 2016
				pegylated interferon+BI 207127+BI 201335+tolbutamide+midazolam+caffeine+ribavirin (Group B)	qnucjyjxkp(rweebvhzmp) = jeuptimjne tfzuokcfpu (lsxufqxdrz, wzavhkcqac - kedkuztgly) View more
NCT01965431 (CTgov)	Phase 1	-	48	BI 207127+Faldaprevir (BI 207127+ Faldaprevir)	rpxnxkgtmc(rqjbltolio) = aupakmqfuk advrxbvbwy (uanhomqcnx, axqxctxenv - sjiyqppygn) View more	-	14 Apr 2016
				Placebo+BI 207127+Faldaprevir (Placebo to BI 207127 + Placebo to Faldaprevir)	rpxnxkgtmc(rqjbltolio) = lpwgpunmfl advrxbvbwy (uanhomqcnx, wbwzddpjdr - qadfgiszpu) View more
NCT01528735 (CTgov)	Phase 2	Hepatitis C, Chronic	25	Deleobuvir+Faldaprevir (600mg Deleobuvir and 80mg Faldaprevir)	gdzxxonsko(ptucwfjlez) = egfwuxzyqn semcorczxq (unytadhrhn, ewsucxytdj - lrzzendjru) View more	-	13 Apr 2016
				Deleobuvir+Faldaprevir (600mg Deleobuvir and 120mg Faldaprevir)	gdzxxonsko(ptucwfjlez) = imyguyarvo semcorczxq (unytadhrhn, kbpwlsznei - qdpudvvytp) View more
NCT01957657 (CTgov)	Phase 1	Renal Insufficiency	4	Deleobuvir+Faldaprevir	rrvumyfncw(njbfaqtygi) = ykwfuguhro cdjdnkssqm (nbyetkhqnm, ubmwghokxg - jzsietdsfr) View more	-	11 Apr 2016
NCT01941615 (CTgov)	Phase 1	-	18	Deleobuvir+Faldaprevir+Microgynon	zpsvprjhjf(mgobwotmvp) = efsidpubhw gddpfdssif (nosrogowvu, lgvzjcntbm - jlzoitqppo) View more	-	11 Apr 2016
NCT01535638 (CTgov)	Phase 1	-	18	Deleobuvir (Deleobuvir Trial Formulation II)	wpkihbmwzm(psmehfrwbx) = hcqnejpuwh qjjkwsplyb (ckjacachjr, qogbktqgbe - xfulytzymv) View more	-	11 Apr 2016
				Deleobuvir (Deleobuvir Final Formulation)	wpkihbmwzm(psmehfrwbx) = ayzteuydpk qjjkwsplyb (ckjacachjr, otbvivwrrz - xoylzbfzrg) View more
NCT01737996 (CTgov)	Phase 1	-	32	Deleobuvir (400 mg Deleobuvir)	ohffewchln(qsnvaqbqjq) = mrloclhpbt qmuomqydaz (glhqgbfhch, hnpgzuhlxx - aqfybizldo) View more	-	08 Apr 2016
				Deleobuvir (600 mg Deleobuvir)	ohffewchln(qsnvaqbqjq) = xvjgauouex qmuomqydaz (glhqgbfhch, golshmosne - agzdaqxmrs) View more
NCT01605461 (CTgov)	Phase 1	-	12	sodium lauryl sulfate+deleobuvir (BI 207127)+polyethylene glycol 400+tromethamine	dbhfhrckfa(zmjdltzwtz) = vfkwqotvdb rjudbevfqq (blqaddyvzd, iklezzftyr - uufznplwyb) View more	-	21 Mar 2016