Identification, preclinical profile, and clinical proof of concept of an orally bioavailable pro-drug of miridesap.

ABSTRACT:

Background and purpose

Miridesap, a depleter of serum amyloid P component (SAP), forms an essential component of a novel approach to remove systemic amyloid deposits; low oral bioavailability necessitates that it is given parenterally. We sought to identify and clinically characterise a pro-drug that preserves the pharmacological properties of miridesap while having adequate oral bioavailability and physical stability.

Experimental approach

We utilised a preclinical screening cascade focused on appropriate physicochemical properties, physical and gut stability, and conversion to miridesap in liver microsomes and blood. GSK3039294 (GSK294) had the desired in vitro profile and progressed to preclinical in vivo pharmacokinetic and safety assessments. Based on a favourable profi

SUBMITTER: Richards D 

PROVIDER: S-EPMC7070169 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature