Fig. 8. Thiazoles enhance binding of BDK to BCKDH complex while thiophenes reduce binding and promote degradation.
A BDK was immunoprecipitated from hearts of DIO mice that were treated with vehicle, 100 mg/kg BT2 QD or 10 mg/kg PF-07247685 BID for 18 days, and proteomics was performed on the immunoprecipitated proteins. Volcano plot demonstrating the most significantly enriched proteins bound to BDK after BT2 treatment (to the left) versus PF-07247585 treatment (to the right). B Representative Western blot of BDK after IgG or BDK immunoprecipitation from mouse hearts (N = 3 animals/group). C An AlphaLISA assay was performed with BDK and BCKDHE2. Fluorescence aligned with in vitro potency of BT2, PF-07208254, PF-07238025 and PF-0724785 (n = 5–26 independent experiments). Source data are provided as a Source Data file.