Delving into the Latest Updates on MGAWN1 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

West Nile virus monoclonal antibody

+ [1]

Target

WNV E protein

Mechanism

WNV E protein inhibitors(WNV E protein inhibitors)

Therapeutic Areas

Infectious DiseasesNervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Acute Flaccid MyelitisMeningitisParalysis+ [2]

Originator Organization

Washington University in St. Louis

Active Organization-

Inactive Organization

MacroGenics, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

The primary purpose of this phase 1, double-blind, cohort study is to evaluate the safety, tolerability, and pharmacokinetics of escalating doses of MGAWN1 administered as a single intravenous (IV) infusion to healthy adults. Subjects will be enrolled sequentially into one of 5 dose-level cohorts, with 8 subjects in each cohort. Six subjects in each cohort will receive MGAWN1 (a Neutralizing, Humanized, Monoclonal Antibody (IgG1k) to West Nile Virus) and 2 will receive a saline control.

Start Date01 Aug 2007

Sponsor / Collaborator

MacroGenics, Inc.

[+1]

100 Clinical Results associated with MGAWN1

Login to view more data

100 Translational Medicine associated with MGAWN1

Login to view more data

100 Patents (Medical) associated with MGAWN1

Login to view more data

13

Literatures (Medical) associated with MGAWN1

01 Oct 2014·Plant Biotechnology JournalQ1 · ENGINEERING & TECHNOLOGY

Structural and functional characterization of an anti‐West Nile virus monoclonal antibody and its single‐chain variant produced in glycoengineered plants

Q1 · ENGINEERING & TECHNOLOGY

ArticleOA

Author: Fuchs, Anja ; Stahnke, Jake ; Loos, Andreas ; Diamond, Michael S. ; Gorlatov, Sergey ; Mehlhop, Erin ; Lai, Huafang ; Hurtado, Jonathan ; He, Junyun ; Chen, Qiang

SummaryPreviously, our group engineered a plant‐derived monoclonal antibody (MAb pE16) that efficiently treated West Nile virus (WNV) infection in mice. In this study, we developed a pE16 variant consisting of a single‐chain variable fragment (scFv) fused to the heavy chain constant domains (CH) of human IgG (pE16scFv‐CH). pE16 and pE16scFv‐CH were expressed and assembled efficiently in Nicotiana benthamiana ∆XF plants, a glycosylation mutant lacking plant‐specific N‐glycan residues. Glycan analysis revealed that ∆XF plant‐derived pE16scFv‐CH (∆XFpE16scFv‐CH) and pE16 (∆XFpE16) both displayed a mammalian glycosylation profile. ∆XFpE16 and ∆XFpE16scFv‐CH demonstrated equivalent antigen‐binding affinity and kinetics, and slightly enhanced neutralization of WNV in vitro compared with the parent mammalian cell‐produced E16 (mE16). A single dose of ∆XFpE16 or ∆XFpE16scFv‐CH protected mice against WNV‐induced mortality even 4 days after infection at equivalent rates as mE16. This study provides a detailed tandem comparison of the expression, structure and function of a therapeutic MAb and its single‐chain variant produced in glycoengineered plants. Moreover, it demonstrates the development of anti‐WNV MAb therapeutic variants that are equivalent in efficacy to pE16, simpler to produce, and likely safer to use as therapeutics due to their mammalian N‐glycosylation. This platform may lead to a more robust and cost‐effective production of antibody‐based therapeutics against WNV infection and other infectious, inflammatory or neoplastic diseases.

01 Sep 2013·ChemMedChemQ3 · MEDICINE

Synthesis and in vitro Evaluation of West Nile Virus Protease Inhibitors Based on the 1,3,4,5‐Tetrasubstituted 1H‐Pyrrol‐2(5H)‐one Scaffold

Q3 · MEDICINE

Article

Author: Lam, Yulin ; Gao, Yaojun ; Samanta, Sanjay ; Cui, Taian

AbstractWest Nile virus (WNV), a member of the Flaviviridae family, is a mosquito‐borne pathogen that causes a large number of human infections each year. There are currently no vaccines or antiviral therapies available for human use against WNV. Therefore, efforts to develop new chemotherapeutics against this virus are highly desired. In this study, a WNV NS2B–NS3 protease inhibitor with a 1,3,4,5‐tetrasubstituted 1H‐pyrrol‐2(5H)‐one scaffold was identified by screening a small library of nonpeptidic compounds. Optimization of this initial hit by the synthesis and screening of a focused library of compounds with this scaffold led to the identification of a novel uncompetitive inhibitor ((−)‐1a16, IC50=2.2±0.7 μM) of the WNV NS2B–NS3 protease. Molecular docking of the chiral compound onto the WNV protease indicates that the R enantiomer of 1a16 interferes with the productive interactions between the NS2B cofactor and the NS3 protease domain and is thus the preferred isomer for inhibition of the WNV NS2B–NS3 protease.

01 Jun 2013·ChemMedChemQ3 · MEDICINE

Synthesis and in vitro Evaluation of West Nile Virus Protease Inhibitors Based on the 2‐{6‐[2‐(5‐Phenyl‐4H‐{1,2,4]triazol‐3‐ylsulfanyl)acetylamino]benzothiazol‐2‐ylsulfanyl}acetamide Scaffold

Q3 · MEDICINE

Article

Author: Sanjay Samanta ; Ting Liang Lim ; Yulin Lam

AbstractIn recent years, clinical symptoms resulting from West Nile virus (WNV) infection have worsened in severity, with an increased frequency in neuroinvasive diseases among the elderly. As there are presently no successful therapies against WNV for use in humans, continual efforts to develop new chemotherapeutics against this virus are highly desired. The viral NS2B‐NS3 protease is a promising target for viral inhibition due to its importance in viral replication and its unique substrate preference. In this study, a WNV NS2B‐NS3 protease inhibitor with a 2‐{6‐[2‐(5‐phenyl‐4H‐[1,2,4]triazol‐3‐ylsulfanyl)acetylamino]benzothiazol‐2‐ylsulfanyl}acetamide scaffold was identified during screening. Optimization of this initial hit by synthesis and screening of a focused compound library with this scaffold led to the identification of a novel uncompetitive inhibitor (1 a24, IC50=3.4±0.2 μM) of the WNV NS2B‐NS3 protease. Molecular docking of 1 a24 into the WNV protease showed that the compound interferes with productive interactions of the NS2B cofactor with the NS3 protease and is an allosteric inhibitor of the WNV NS3 protease.

100 Deals associated with MGAWN1

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute Flaccid Myelitis	Phase 2	-	MacroGenics, Inc.	01 May 2009
Meningitis	Phase 2	-	MacroGenics, Inc.	01 May 2009
Paralysis	Phase 2	-	MacroGenics, Inc.	01 May 2009
West Nile Fever	Phase 2	-	MacroGenics, Inc.	01 May 2009
Virus Diseases	Phase 2	US	MacroGenics, Inc.	01 Aug 2007