Mubritinib, a novel AML lead compound currently in lead optimization phase!
Through a chemical screen in sequenced primary AML specimens of the Leucegene cohort, we identified mubritinib, a known ERBB2 inhibitor, to be selectively toxic against a large subset of poor outcome AML specimens that exhibit oxidative phosphorylation hyperactivity. In this AML population, Mubritinib appears to act as a direct and ubiquinone-dependent ETC complex I inhibitor with strong in vitro and in vivo anti-leukemic activity (Baccelli et al., Cancer Cell 2019).
This ubiquinone-dependent NADH dehydrogenase inhibitor is currently in lead optimization phase.
HMGA2 AML prognostic test developed and validated
We analyzed RNA sequencing data of 430 clinically annotated AML samples and identified HMGA2 as a new candidate prognostic marker. This marker was successfully developed and validated as an RT-qPCR test to facilitate implementation in clinical laboratories. High HMGA2 expression adds significant independent prognostic value to known clinical and genetic prognostic factors in AML, and is predictive of poor clinical outcomes with standard AML therapies (Compound Correlation Clusters - CCCs
We developed a novel approach, which we named Compound Correlation Clusters (CCCs) that efficiently refines synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens.Characterization of Leucegene AML cohort
Identification of UM729
