Evaluations employing DEREK and P450 in silico metabolism indicate that slight alterations or replacements in the pyrrolidine moiety (98%) through drug development may improve the metabolic stability of novel derivatives relative to fedratinib.
Metabolic stability research showed crenolanib's moderate extraction ratio. In silico software suggested that small piperidin-4-amine moiety alterations (99%) during drug development may improve metabolic stability.
Metabolic stability studies demonstrated moderate baricitinib extraction ratio. Minor adjustments to the pyrrole (88%) and pyrimidine (5%), during drug design, may increase novel derivatives' safety and metabolic stability compared to baricitinib.
Veliparib exhibited a relatively slow extraction ratio, with a low Clint of 22.23 mL min−1 kg−1 and a long t1/2 of 36.48 min. Minor replacements within the pyrrolidine ring (96%) in veliparib may increase the metabolic stability and safety profile.
An UPLC-MS/MS method was established for assessing avapritinib in HLMs matrix. In silico analysis suggests that minor structural changes to the methyl pyrazole moiety in drug design may improve the metabolic stability relative to avapritinib.