BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Carnitine palmitoyl transferase 1 (CPT1); CPT2; v-myc myelocytomatosis viral oncogene homolog (MYC; c-Myc)

March 10, 2016 8:00 AM UTC

Patient sample, mouse and cell studies suggest inhibiting CPT1 or CPT2 could help treat MYC-driven triple-negative breast cancer (TNBC). In TNBC patients, low tumor levels of acetyl-coenzyme A carboxylase β (ACACB; ACC2), a negative regulator of CPT1 and CPT2, correlated with poor survival. In multiple human MYC-driven TNBC cell lines, CPT2 knockdown decreased cell proliferation compared with normal CPT2 expression. In a xenograft mouse model of MYC-overexpressing TNBC, a CPT1 inhibitor tool compound decreased tumor growth compared with vehicle. In an orthotopic patient-derived xenograft mouse model of MYC-overexpressing TNBC, the CPT1 inhibitor decreased tumor growth and increased survival. Next steps could include inhibiting CPT1 or CPT2 in other models of MYC-driven cancer.

Heart Metabolics Ltd. has perhexiline, a small molecule inhibitor of CPT1 and CPT2, in Phase II to treat cardiomyopathy. ...