BTM-3528 is an activator of the mitochondrial protease OMA1 with anticancer activity.BTM-3528 activates the ISR via the mitochondrial protease OMA1, inducing OMA1-dependent cleavage of DELE1 and OPA1 and mitochondrial fragmentation.BTM-3528 induces cell growth arrest and apoptosis.

Both BTM-3528 and BTM-3566 demonstrated potent, dose-dependent activity against DLBCL lines of varying genotypes, including MYC-rearranged (“double” and “triple” hit) lymphomas, with growth inhibition and IC >90%50 values ​​of 0.16–0.57 μmol/L. [2]

METHODS: BTM-3566 was tested in 9 human DLBCL patient-derived xenograft (PDX) models representing ABC and GCB DLBCL subtypes, treated with 20 mg/kg BTM-3566.
RESULTS: All 3 mice in 6 of the 9 PDX models achieved CR, and when 27 mice from the treatment groups across the 9 models were combined, CR was observed in 66% (19/27), with an additional 4 mice experiencing partial remission (PR), 2 mice experiencing stable tumors, and 2 experiencing progressive disease. [2]