NN1177 (100 nM, 3 days) TFA reduces CYP3A4 mRNA expression (57.2-71.7%) and activity (18.5-51.5%) in freshly isolated human hepatocytes[3].
NN1177 (3 or 5 nmol/kg, s.c.) TFA induces body weight loss, loss of fat mass, and improvement in glucose tolerance in diet-induced obese (DIO) mice[1].
NN1177 (0.75-4 nmol/kg, s.c., once daily, 8 weeks) TFA reduces liver fat and inflammatory and fibrosis relevant biomarkers in C57Bl/6 mice fed a fructose and high fat rich diet (NASH model)[2].
References:
[1]. Simonsen L, et al. Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: Translational difficulties and pitfalls. PLoS One. 2022 Mar 4;17(3):e0264974.
[2]. Monfeuga T, et al. Evaluation of long acting GLP1R/GCGR agonist in a DIO and biopsy-confirmed mouse model of NASH suggest a beneficial role of GLP-1/glucagon agonism in NASH patients. Mol Metab. 2023 Dec 7;79:101850.
[3]. Säll C, et al. In vitro CYP450 enzyme down-regulation by GLP-1/glucagon co-agonist does not translate to observed drug-drug interactions in the clinic. Drug Metab Dispos. 2022 Jun 9:DMD-AR-2022-000865.