Pognan, Francois, Timsit, Yoav, Wolf, Armin, Couttet, Philippe, Buono, Chiara and Galarneau, Jean-Rene (2022) Liver enzyme delayed clearance in rat treated by CSF1 receptor specific antagonist Sotuletinib. Current Research in Toxicology, 3.

Abstract

Sotuletinib (BLZ945), a CSF1-R specific kinase inhibitor developed for the treatment of Amyotrophic Lateral Sclerosis, induced liver enzyme elevation in absence of hepatic lesions in preclinical rat and monkey studies. The depletion of Kupffer cells through CSF1 pathway inhibition has been hypothesized as responsible for this effect. However, a release of these biomarkers from unseen hepatic lesions or from other organs cannot be excluded. Here we demonstrate a delayed clearance independently of any potential organ lesions by exogenously injecting recombinant his-Tagged ALT1 into rats pretreated with Sotuletinib, excluding a potential undetected cytotoxic effect.

Item Type:	Article
Keywords:	Amyotrophic Lateral Sclerosis; Colony Stimulating Factor 1; ALT clearance; BLZ945; Sotuletinib
Date Deposited:	16 Nov 2022 00:45
Last Modified:	16 Nov 2022 00:45
URI:	https://oak.novartis.com/id/eprint/47755