BI-11634 free base

BI-11634 (1 μM; 60 min; HLM) free base metabolism is inhibited by 95% by the CYP3A4 inhibitor Ketoconazole (HY-B0105) (3 μM) and by 49% by Quinidine (HY-B1751) (3 μM), supporting a major role of CYP3A4 in BI-11634 metabolism^[1].
BI-11634 (1 μM; 60 min; recombinant CYP1A2/CYP2C9/CYP2C19/CYP2D6/CYP3A4) free base recombinant CYP phenotyping shows that, after normalization to relative hepatic content, CYP3A4 contributes approximately 99% to BI-11634 free base metabolism, indicating that BI-11634 free base is predominantly metabolized by CYP3A4^[1].
When BI-11634 (1 μM; 60 min; rCYP3A4) free base is co-incubated with Quinidine (3 μM), BI-11634 free base metabolism decreases by 69%, confirming that the inhibition of BI-11634 metabolism by Quinidine in HLM primarily involves CYP3A4^[1].
In substrate depletion assays of BI-11634 (0.305-313 μM; 60 min) free base in HLM and rCYP3A4, the apparent K_m values for its metabolism are 23 μM and 7.6 μM, respectively^[1].
BI-11634 free base exhibits a CYP3A4 metabolic interaction pattern distinct from that of midazolam and testosterone, but more similar to that of Nifedipine (HY-B0284). The results support that BI-11634 free base may interact with an alternative binding site of CYP3A4, although its association with the Nifedipine binding site has not been definitively demonstrated^[1].