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In vitro biomimetic HPLC and in vivo characterisation of GM6, an endogenous regulator peptide drug candidate for amyotrophic lateral sclerosis

Klara Valko orcid id ; Bio-Mimetic Chromatography Ltd, Business & Technology Centre, Stevenage, SG1 2DX United Kingdom
Mark Kindy ; Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA
James Evans ; PhenoVista, San Diego, CA, USA
Dorothy Ko ; Genervon Biopharmaceuticals LLC, Pasadena, CA, USA

Puni tekst: engleski pdf 952 Kb

str. 176-189

preuzimanja: 537



Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease of the human motor system. Subunits of the 33-amino acid containing motorneurontrophic factor (MNTF) have been investigated and GM6 has been found as a potential peptide therapeutic for ALS. This linear peptide drug candidate has been characterized by HPLC based physicochemical and biomimetic measurements to estimate its in vivo distribution behavior and to estimate its cell penetration and brain to plasma concentration ratio. The free tissue concentration vs time profile has been estimated using the measured physicochemical and biomimetic properties of the intact GM6 molecules and its microsomal stability. The in vitro and in vivo measurements supported the estimated in vivo distribution behavior of GM6.

Ključne riječi

motoneuron degeneration; peptide drug candidate; ADME of peptide drugs; biomimetic properties; PK profile; free tissue concentration vs time PK

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