BRD-810 is a highly selective MCL1 inhibitor (Kd=0.3 nM) capable of inducing tumour cell apoptosis, suitable for studying haematological malignancies and solid tumours. BRD-810 binds the BH3 groove of MCL1, activates Caspase, and disrupts the MCL1-BAK complex in cancer cells (IC50=1.2 nM).

MCL1:0.3 nM (Kd), Caspase-3:66 nM (EC50)

BRD-810 demonstrates potent antiproliferative effects across various solid tumor and hematologic malignancy models, including breast cancer, lung cancer, melanoma, sarcoma, lymphoma, and leukemia. For instance, its IC₅₀ values against SU-DHL-10, AMO-1, DMS114, and HCC-1187 are 0.1 nM, 0.3 nM, 0.6 nM, and 0.9 nM, respectively [1].
In HMC1-8 cells, BRD-810 (1 nM–1 μM) dose-dependently activates caspase 3 and induces cell death, with an EC₅₀ of 66 nM for caspase activation and an IC₅₀ of 63 nM for growth inhibition [1].
BRD-810 (0–1 μM, acting for 5 minutes to 72 hours) rapidly triggers irreversible apoptosis in MCL1-dependent cancer cell lines. However, prolonged high-concentration exposure Results in significant cardiotoxicity in Homo sapiens-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) [1].

In multiple mouse models of hematologic and solid tumors, BRD-810 demonstrated significant antitumor activity when administered intravenously at doses of 3–50 mg/kg, either as a single dose or via weekly continuous dosing for 21–60 days, alone or in combination with other regimens. Furthermore, no cardiac toxicity signals were detected for BRD-810 in safety studies conducted in beagle dogs.[1]