SRC-3
SRC-3/NCOA3/AIB1 is a p160 nuclear receptor coactivator that bridges nuclear receptors and transcription factors to chromatin-regulating coactivator complexes, thereby supporting transcriptional activation[1]. Mechanistically, SRC-3 regulates ERα, AP-1, E2F, NF-κB, and TEAD-dependent gene programs, linking hormone signaling, inflammatory transcription, proliferation, and oncogenic gene expression[1][2]. In breast cancer models, SRC-3 promotes ERα-positive tumor biology, endocrine resistance, and XBP1-associated unfolded protein response signaling through the PERK-ATF4 pathway[3][4]. Compared with related p160 isoforms, NCOA3 shows selective recruitment to the PLAC1 promoter in ERα-positive MCF-7 cells, whereas NCOA1 and NCOA2 do not show this recruitment pattern[5]. In stem-cell models, Ncoa3 also acts as an essential Esrrb coactivator that sustains embryonic stem-cell self-renewal and reprogramming[6]. For experimental applications, SRC-3 inhibition by bufalin reduced TNBC cell viability and motility, while 3-phospho-bufalin inhibited tumor growth in an orthotopic TNBC mouse model[7].
References:
- [1]. Kushner MH, et al. The AIB1/NCOA3/SRC-3 Oncogene. InOncogenes and Carcinogenesis 2018 Nov 5. IntechOpen.
- [2]. Shrestha A, et al. Phosphorylation of steroid receptor coactivator-3 (SRC-3) at serine 857 is regulated by the p38MAPK-MK2 axis and affects NF-κB-mediated transcription. Sci Rep. 2020 Jul 9;10(1):11388. [Content Brief]
- [3]. Kiliti AJ, et al. AIB1/SRC-3/NCOA3 function in estrogen receptor alpha positive breast cancer. Front Endocrinol (Lausanne). 2023 Aug 30;14:1250218. [Content Brief]
- [4]. Gupta A, et al. NCOA3 coactivator is a transcriptional target of XBP1 and regulates PERK-eIF2α-ATF4 signalling in breast cancer. Oncogene. 2016 Nov 10;35(45):5860-5871. [Content Brief]
- [5]. Wagner M, et al. NCOA3 is a selective co-activator of estrogen receptor α-mediated transactivation of PLAC1 in MCF-7 breast cancer cells. BMC Cancer. 2013 Dec 4;13:570. [Content Brief]
- [6]. Percharde M, et al. Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming. Genes Dev. 2012 Oct 15;26(20):2286-98. [Content Brief]
- [7]. Song X, et al. Steroid Receptor Coactivator-3 (SRC-3/AIB1) as a Novel Therapeutic Target in Triple Negative Breast Cancer and Its Inhibition with a Phospho-Bufalin Prodrug. PLoS One. 2015 Oct 2;10(10):e0140011. [Content Brief]
-
SRC-3 Related Products (3)
-
EGFR/c-SRC-IN-1
0 ImagesCat. No.: HY-184274EGFR/c-SRC-IN-1 is a blood-brain barrier-impermeable, ATP-competitive dual-target inhibitor of EGFR/c-SRC, with an IC50 of 0.05 μM against EGFR and an IC50 of 0.07 μM against c-SRC. EGFR/c-SRC-IN-1 shows selectivity toward ABL-2 and VEGFR-2 kinases. EGFR/c-SRC-IN-1 triggers endogenous apoptosis by upregulating p53 and Bax, downregulating Bcl-2, and altering the Bax/Bcl-2 ratio. EGFR/c-SRC-IN-1 can be used in the research of non-small cell lung cancer, hepatocellular carcinoma, and triple-negative breast cancer.
-
SI-2
0 ImagesCat. No.: HY-101447CAS No.: 223788-33-8Synonyms: EPH 116SI-2 (EPH 116) is an inhibitor for steroid receptor coactivator-3 (SRC-3), which reduces the transcriptional activity and protein concentration of SRC-3 in cells, exhibits cytotoxicity in cancer cell, inhibits migration of MDA-MB-468, induces apoptosis of MDA-MB-468. SI-2 inhibits the tumor growth in mouse models, without significant toxicity for heart and other major organs (20 mg/kg).
-
BY13
0 ImagesCat. No.: HY-176225BY13 is a SRC-3 PROTAC degrader with a DC50 of 0.031 μM. BY13 selectively blocks the ER signaling pathway over that of androgen receptor (AR)) through down-regulating ERα level. BY13 potently overcomes endocrine resistance in breast cancer by inducing cell cycle arrest in G1 phase and apoptosis, with superior effect over Fulvestrant (HY-13636). BY13 significantly inhibits the growth of drug-resistant breast tumors without obvious toxicity in LCC2 xenograft mice model.
