MYCi975 is a small molecule inhibitor of c-Myc [1]. MYCi975 can directly bind to c-Myc protein, block its heterodimer formation with Max, and promote phosphorylation and protein degradation of c-Myc at Thr58, thereby inhibiting c-Myc-driven transcriptional activity and cancer cell proliferation [2-3]. MYCi975 is commonly used to treat cancer [4].
In HS578T cells, MYCi975 (10μM; 48h) treatment induced apoptosis in up to 80% of cells after 48 h of incubation [5]. In MDA-MB-231 cells, combination treatment of COTI-2 and MYCi975 (0.16-10μM; 5d) produced a synergistic growth inhibitory effect on cells [6]. In A549 cells, combination of MYCi975 (2.5-10μM; 72h) and TMP269 significantly reduced the viability of NSCLC cell lines [7].
In head and neck squamous cell carcinoma (HNSCC) nude mouse model, MYCi975 (100mg/kg; ip; 4 weeks) alone or MYCi975 plus cisplatin significantly reduced lymph node metastasis [8]. In both HNSCC xenograft and syngeneic murine models, MYCi975(100mg/kg; ip; 4 weeks) inhibited HNSCC growth [9].
References:
[1]. Makii R, Ned T, Underdown MJ, et al. 582 A comparative approach to understanding the role of oncogenic MYC signaling in the metastatic osteosarcoma tumor immune microenvironment. Journal of Clinical and Translational Science. 2025 Apr 1; 9(s1): 171.
[2]. Holmes AG, Parker JB, Sagar V, et al. A MYC inhibitor selectively alters the MYC and MAX cistromes and modulates the epigenomic landscape to regulate target gene expression. Science Advances. 2022 Apr 27; 8(17): eabh3635.
[3]. Vízkeleti L, Spisák S. Rewired metabolism caused by the oncogenic deregulation of MYC as an attractive therapeutic target in cancers. Cells. 2023 Jun 29; 12(13): 1745.
[4]. Whitfield JR, Soucek L. MYC in cancer: from undruggable target to clinical trials. Nature Reviews Drug Discovery. 2025 Feb 19: 1-3.
[5]. Tang M, O’Grady S, Crown J, et al. MYC as a therapeutic target for the treatment of triple-negative breast cancer: preclinical investigations with the novel MYC inhibitor, MYCi975. Breast Cancer Research and Treatment. 2022 Sep; 195(2): 105-115.
[6]. Tang M, Crown J, Duffy MJ. Degradation of MYC by the mutant p53 reactivator drug, COTI-2 in breast cancer cells. Investigational New Drugs. 2023 Aug; 41(4):5 41-550.
[7]. Park J, Chen YY, Cao JJ, et al. MYC plus class IIa HDAC inhibition drives mitochondrial dysfunction in non-small cell lung cancer. Cell Reports. 2025 Jun 24; 44(6).
[8]. Liu S, Qin Z, Mao Y, et al. Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma. Theranostics. 2024 Jan 1; 14(2): 622.
[9]. Liu S, Qin Z, Mao Y, et al. Therapeutic targeting of MYC in head and neck squamous cell carcinoma. Oncoimmunology. 2022 Dec 31; 11(1): 2130583.
MYCi975是一种c-Myc小分子抑制剂 [1]。MYCi975可以直接结合c-Myc蛋白，阻断其与Max形成异二聚体，并促进c-Myc在Thr58位点的磷酸化和蛋白质降解，从而抑制c-Myc 驱动的转录活性和癌细胞增殖 [2-3]。MYCi975常用于治疗癌症 [4]。
在HS578T细胞中，MYCi975（10μM；48h）处理48h后，诱导高达80%的细胞凋亡 [5]。在MDA-MB-231细胞中，COTI-2和MYCi975（0.16-10μM；5d）联合处理对细胞产生协同生长抑制作用 [6]。在A549细胞中，MYCi975（2.5-10μM；72h）与TMP269联合应用显著降低了非小细胞肺癌（NSCLC）细胞系的活力 [7]。
在头颈部鳞状细胞癌（HNSCC）裸鼠模型中，MYCi975（100mg/kg；ip；4周）单独给药或MYCi975联合顺铂给药均显著降低了淋巴结转移 [8]。在HNSCC异种移植和同基因小鼠模型中，MYCi975（100mg/kg；ip；4周）均抑制了HNSCC的生长 [9]。