Design, synthesis and biological evaluation of a series of FGFRs-dominant multi-target receptor tyrosine kinase inhibitors for the treatment of gastric cancer. The pharmacokinetic analysis was performed by Medicilon

Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype. ClpP is a component of the ClpXP protein complex localized in the mitochondrial matrix. Modifiers of ClpP activity have demonstrated anti-cancer properties. TR-107 is a potent chemical activator of the human mitochondrial protease ClpP, with excellent potency, specificity and drug-like properties. TR‐107 shows ClpP‐dependent growth inhibition in the low nanomolar range that is equipotent to Paclitaxel in TNBC cell models. The pharmacokinetic properties of TR‐107 were compared with other known ClpP activators including ONC201 and ONC212. TR‐107 displayed excellent exposure and serum t1/2 after oral administration. Pharmacokinetic analysis were evaluated for pharmacokinetic properties in ICR mice by Medicilon.

Age-related neurodegenerative disorders are characterized by the progressive accumulation of misfolded and aggregated proteins. SNARE protein ykt6 plays a crucial role in proteostasis and lysosomal function by enhancing hydrolase trafficking under stressful conditions. Activating ykt6 by small-molecule farnesyltransferase inhibitors (FTIs) restores lysosomal activity and reduces a-synuclein in patient-derived neurons and mice. Pharmacokinetic studies revealed that after a single oral dose, the FTI (LNK-754) was cleared from plasma within 20 hours and could rapidly cross the blood-brain-barrier. Pharmacokinetic analysis was performed as a service provided by Medicilon.