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When Faecalibacterium prausnitzii was incubated with tacrolimus, we noticed the formation of two compounds, with the primary one being identified as M1. Interestingly, this transformation was absent when tacrolimus was incubated with hepatic microsomes. By isolating, purifying, and analyzing the structure through mass spectrometry and nuclear magnetic resonance spectroscopy, we concluded that M1 is a C-9 keto-reduction product of tacrolimus.
Pharmacological testing conducted on human peripheral blood mononuclear cells demonstrated that M1 exhibits significantly lower potency as an immunosuppressant compared to tacrolimus, being 15 times less effective. Furt…