New drug triggers rapid cell death in cancer models while sparing healthy cells, may also fight resistant cancers

Good news! Cancer is history (soon)!

"...  compound called BRD-810 that holds promise as a therapeutic candidate for cancer. This small molecule reactivates the apoptosis cascade in tumor cells while sparing healthy cells in animal models. ...

Apoptosis, or programmed cell death, is a natural end process for all cells. But many cancers have mechanisms to block this cascade, allowing them to proliferate dangerously. BRD-810 restores the normal apoptotic process by inhibiting a protein called MCL1, which normally protects cells from apoptosis. MCL1 is one of the most highly overexpressed proteins in many cancer types, particularly those that are resistant to standard chemotherapies — making it an attractive drug target. ...

compound binds to MCL1, removing its protective effects and triggering cell death in cancer. Importantly, unlike other MCL1 inhibitors that have raised concerns about cardiovascular side effects in early-stage clinical trials, BRD-810 acts quickly within cancer cells and is eliminated from the body in animal models within a few hours. This rapid clearance minimizes the drug’s potential impact on healthy cells. ..."

From the abstract:

"The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition. BRD-810 induced rapid cell killing within 4 h in vitro but, in the same 4-h window, had no impact on cell viability or troponin I release in human induced pluripotent stem cell-derived cardiomyocytes, even at suprapharmacologic concentrations. In vivo BRD-810 induced efficacy in xenograft hematological and solid tumor models despite the short residence time of BRD-810 in plasma. In totality, our data support the hypothesis that short-term inhibition of MCL1 with BRD-810 can induce apoptosis in tumor cells while maintaining an acceptable safety profile. We, therefore, intend to advance BRD-810 to clinical trials."

New drug triggers rapid cell death in cancer models | Broad Institute "BRD-810 inhibits the MCL1 protein and reactivates apoptosis in tumor cells, displaying therapeutic potential in animal models."

BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models (open access)

Fig. 1: BRD-810 is a potent and selective inhibitor of the antiapoptotic protein MCL1.