Fig. 7: mTORC1 inactivation mediates cardiotoxicity of MCL1 inhibition and can be ameliorated by leucine supplementation.
From: MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis
A Serum levels of cardiac-specific Troponin T of humanized Mcl-1 mice (n = 4 mice per group) treated for three weeks with Vehicle or ABBV-467 (25 mg/kg or 12.5 mg/kg administrated by I.V. injection on a Q7D × 3 schedule) alone or in the indicated combinations with supplementation of Leucine (150 mmol/L in the drinking water) and treatment with Rapamycin (2 mg/kg I.P. three times a week). (n = 4 mice per group). B Mitochondrial OCR of hearts isolated from (A) and immediately sliced, placed in Agilent Seahorse XF24 Islet Capture Microplate and measured by Seahorse XF24 metabolic Analyzer. (n = 4 mice per group). C Immunoblotting of lysate derived from the hearts of mice in A. The samples derived from the same experiment but different gels for pS6 and pS6K, another for S6K1 and another for S6 were processed in parallel. D Schematic representation (generated by biorender.com) of the model of MCL-1-mediated regulation of mTORC1 and bioenergetics and the effect of MCL1 inhibitors. Statistics are derived from 4 biological replicates. Data is presented as mean +/- SD and significance is determined by unpaired two-tailed t-test. Created in BioRender. Elgendy, M. (2025) https://BioRender.com/37rx81t and Elgendy, M. (2025) https://BioRender.com/rydxylv.
