What question did this study set out to answer?

To evaluate the therapeutic efficacy and molecular mechanism of FT-6876, a selective CBP/p300 bromodomain inhibitor, in preclinical in vitro and in vivo models of androgen receptor-positive breast cancer.

February 24, 2023Targeted OncologyOpen Access

FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer

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Authors

MCMaureen CaligiuriForma Therapeutics (United States)GWGrace L. WilliamsForma Therapeutics (United States)JCJennifer CastroForma Therapeutics (United States)

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Implication

Preclinical study demonstrates tumor growth inhibition by FT-6876 in androgen receptor-positive breast cancer models, indicating therapeutic potential for receptor-dependent subtypes.

Key Points

To evaluate the therapeutic efficacy and molecular mechanism of FT-6876, a selective CBP/p300 bromodomain inhibitor, in preclinical in vitro and in vivo models of androgen receptor-positive breast cancer.
Assessed mechanistic effects on chromatin and transcription using chromatin immunoprecipitation (ChIP), precision run-on sequencing (PRO-seq), and H3K27 acetylation profiling.
Evaluated antiproliferative activity and tumor growth inhibition across in vitro cell models and in vivo androgen receptor-positive triple-negative and estrogen receptor-positive breast cancer models.
FT-6876 selectively displaced CBP/p300 from chromatin, diminished H3K27 acetylation at specific promoter sites, and reduced nascent RNA, enhancer RNA, and androgen/estrogen receptor target gene expression.
In vitro antiproliferative activity occurred in a time- and concentration-dependent manner that directly correlated with cellular androgen receptor expression levels.
In vivo administration achieved consistent tumor growth inhibition in both androgen receptor-positive triple-negative and estrogen receptor-positive breast cancer subtypes alongside favorable pharmacokinetics.

Cite This Study

Caligiuri et al. (2023) studied this question.

synapsesocial.com/papers/6aa4290922af0bded4f4396e https://doi.org/10.1007/s11523-023-00949-7

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Implication

Preclinical study demonstrates tumor growth inhibition by FT-6876 in androgen receptor-positive breast cancer models, indicating therapeutic potential for receptor-dependent subtypes.

FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer

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Implication

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Cite This Study

FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer

Discussion

Member takes

Implication

Key Points

Cite This Study

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