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Nuclear receptor coactivator 1 (SRC-1) is a member of the p160 family of transcriptional coregulators that plays a fundamental role in mediating the actions of nuclear receptors and other transcription factors [2, 3]. It functions by recruiting chromatin-modifying enzymes, such as histone acetyltransferases, to promoter regions, thereby enhancing the transcription of target genes involved in hormone signaling, metabolism, and cell growth [2, 3, 6]. SRC-1 is highly expressed in various tissues, including the brain and reproductive organs, and is essential for normal development and physiological homeostasis [2, 7]. In many cancers, particularly breast and prostate cancer, SRC-1 is frequently overexpressed and serves as a key driver of tumor progression, metastasis, and resistance to endocrine therapies [11, 15]. Because of its central role in integrating multiple oncogenic signaling pathways, SRC-1 is considered a high-value therapeutic target [1, 10]. Small molecule inhibitors and modulators, such as gossypol and MCB-613, are being developed to disrupt its interactions with nuclear receptors and inhibit its pro-tumorigenic activities [1, 10].
Inhibition of coactivator recruitment to nuclear receptors, reduction of cellular protein concentrations through degradation, and blocking of the interaction between the coactivator and the receptor-interacting domain.
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