Acute Myeloid Leukemia Coverage From Every Angle

Preclinical Study of Novel Dual Inhibitor of BET-CBP/p300 in AML

By: Sarah Campen, PharmD
Posted: Monday, August 16, 2021

A novel oral agent, NEO2734, is under study for potential clinical development in the treatment of patients with acute myeloid leukemia (AML), according to preclinical research published in HemaSphere. “Our findings highlight the efficacy of NEO2734 in elimination of primary AML cells, leukemic progenitors and leukemic stem cells, and in reducing leukemic cell load in combination with chemotherapy treatment in AML patients,” stated Linda Smit, PhD, of the Amsterdam University Medical Center, the Netherlands, and colleagues.

Unlike single epigenetic inhibitors, which the authors noted have shown limited efficacy due to resistance and lack of effective elimination of leukemic stem cells, NEO2734 is a dual epigenetic inhibitor. It inhibits bromodomain and extraterminal domain (BET) proteins, cyclic AMP response binding protein-binding protein (CBP), and the E1A-interacting protein of 300 kDa (p300).

This study evaluated the biologic activity of two inhibitors targeting both the BET and CBP/p300 proteins, NEO2734 and NEO1132. Both agents had activity against AML cell lines by inducing apoptosis in the leukemic blasts and effectively downgraded c-Myc and Bcl2 expression.

In mice models, NEO2734 also reduced leukemic engraftment alone and in combination with chemotherapy—in contrast, NEO1132 did not significantly reduce leukemic burden or engraftment. As for toxicity, it appeared that NEO2734 did not affect the survival of normal hematopoietic cells and was well tolerated in mice.

“Dual inhibition of BET and CBP/p300 using NEO2734 is a promising therapeutic strategy for AML patients, making it a focus for clinical translation,” the study authors concluded.

Disclosure: For full disclosures of the study authors, visit

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