GSK1379725A (AU1)is a selective BPTF (bromodomain PHD finger transcription factor) ligand with a binding affinity (Kd) of 2.8µM[1-2]. GSK1379725A can be used to study the role of BPTF in the mechanism of cancer development and progression[3-4].
In vitro, 4T1 and E0771-LMB triple-negative breast cancer cells were pretreated with GSK1379725A (2.5µM) for 12 hours, followed by co-treatment with chemotherapeutic drugs (such as vinorelbine, vinblastine, doxorubicin, etc.) for 96 hours. GSK1379725A significantly enhanced the cytotoxic effects of the chemotherapeutic agents on the cells and induced apoptosis and senescence[5]. K562 (chronic myeloid leukemia cells) and MCF-7 (hormone-positive breast cancer cells) were treated with GSK1379725A (5µM) for 72 hours. GSK1379725A significantly inhibited cell viability[6].
In vivo, BALB/c nude mice implanted with METTL14-/- Luc-Renca renal cancer cells (a murine renal cancer cell line) were treated with GSK1379725A (13.2mg/kg) via intraperitoneal injection three times per week for 5 weeks. GSK1379725A significantly inhibited distal lung metastasis of METTL14-deficient renal cancer cells and improved the survival prognosis of tumor-bearing mice[7]. BALB/c nude mice bearing subcutaneous xenografts of MGC803 gastric cancer cells were treated with GSK1379725A (5mg/kg) via intraperitoneal injection once daily for 30 days. GSK1379725A monotherapy significantly inhibited tumor growth and demonstrated synergistic antitumor effects when combined with Erlotinib (20mg/kg)[8].
References:
[1] Urick AK, Hawk LM, Cassel MK, et al. Dual Screening of BPTF and Brd4 Using Protein-Observed Fluorine NMR Uncovers New Bromodomain Probe Molecules. ACS Chem Biol. 2015 Oct 16;10(10):2246-56.
[2] Tyutyunyk-Massey L, Sun Y, Dao N, et al. Autophagy-Dependent Sensitization of Triple-Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of the Nucleosome Remodeling Factor. Mol Cancer Res. 2021 Aug;19(8):1338-1349.
[3] Jiang C, Yang Y, He S, et al. BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma. Biol Proced Online. 2023 May 11;25(1):11.
[4] Gao S, Zhang W, Ma J, et al. PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer. J Transl Med. 2023 Mar 26;21(1):220.
[5] Sinanian MM, Rahman A, Elshazly AM, et al. A BPTF Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Murine Triple-Negative Breast Cancer Cells to Chemotherapy. Int J Mol Sci. 2024 Oct 22;25(21):11346.
[6] Kirberger SE, Ycas PD, Johnson JA, et al. Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor. Org Biomol Chem. 2019 Feb 13;17(7):2020-2027.
[7] Zhang C, Chen L, Liu Y, et al. Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. Theranostics. 2021 Jan 26;11(8):3676-3693.
[8] Li F, Yu J, Pan T, et al. BPTF Drives Gastric Cancer Resistance to EGFR Inhibitor by Epigenetically Regulating the C-MYC/PLCG1/Perk Axis. Adv Sci (Weinh). 2023 Dec;10(34):e2303091.
GSK1379725A (AU1)是一种选择性BPTF（溴结构域PHD指转录因子）配体，其结合亲和力（Kd）为2.8μM[1-2]。GSK1379725A可用于研究BPTF中癌症发生发展中的作用机制[3-4]。
在体外，GSK1379725A（2.5μM）预处理4T1和E0771-LMB三阴性乳腺癌细胞12小时，随后与化疗药物（如长春瑞滨、长春碱、多柔比星等）共同处理96小时。GSK1379725A显著增强化疗药物对细胞的毒性作用，并诱导细胞凋亡和衰老[5]。GSK1379725A(5μM)处理K562（慢性髓系白血病细胞）和MCF-7（激素阳性乳腺癌细胞）72小时。GSK1379725A显著抑制细胞活力 [6]。
在体内，GSK1379725A（13.2mg/kg）每周三次腹腔注射，用于处理植入METTL14-/- Luc-Renca肾癌细胞（小鼠肾癌细胞系）的BALB/c裸鼠，持续5周。GSK1379725A显著抑制了METTL14缺陷肾癌细胞的远端肺转移，并改善了荷瘤小鼠的生存预后[7]。GSK1379725A（5mg/kg）每日一次腹腔注射，用于处理携带MGC803胃癌细胞皮下移植瘤的BALB/c裸鼠，持续30天。GSK1379725A单药治疗显著抑制了肿瘤生长，并且与厄洛替尼（20mg/kg）联合使用时表现出协同抗肿瘤效应[8]。