Remodelin is a small molecule inhibitor of N-acetyltransferase 10 (NAT10).Dysregulation of N-acetyltransferase 10 (NAT10) is associated with the development of many types of tumors[1].
Combined remodelin and doxorubicin treatment reduced cell viability significantly more compared to cells treated with doxorubicin alone. EDU assays confirmed that both doxorubicin and remodelin decreased breast cancer cell proliferation more compared to cells treated with doxorubicin alone, suggesting remodelin attenuates doxorubicin resistance in breast cancer cells (MDA-MB-231)[2]
Remodelin was given daily by intragastric administration for 4 weeks. PDX model tumour volume was recorded and TGI was calculated. As a result, Remodelin significantly inhibited the growth of HNSCC PDXs in vivo[3]
The treatment of Remodelin could suppress the growth of cancer cells but not induce apoptosis, that Remodelin has little cytotoxicity. Remodelin significantly reduced AR-negative prostate cancer tumor growth. The anti-neoplastic effects of Remodelin through NAT10 inhibition should be credited to the slowing down of DNA replication, which could consequently attenuate replication stress-associated genomic instability, and ultimately delay the progression of prostate cancer[4]
References:
[1]. Ma R, Chen J, et al. Up regulation of NAT10 promotes metastasis of hepatocellular carcinoma cells through epithelial-to-mesenchymal transition.
[2]. Wu J, Zhu H, et al. Inhibition of N-acetyltransferase 10 using remodelin attenuates doxorubicin resistance by reversing the epithelial-mesenchymal transition in breast cancer. Am J Transl Res. 2018 Jan 15;10(1):256-264.
[3]. Tao W, Tian G, et al. NAT10 as a potential prognostic biomarker and therapeutic target for HNSCC. Cancer Cell Int. 2021 Aug 6;21(1):413.
[4]. Ma N, Liu H, et al.Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication. Int J Mol Sci. 2022 Jun 12;23(12):6573.
Remodelin 是 N-乙酰转移酶 10 (NAT10) 的小分子抑制剂。N-乙酰转移酶 10 (NAT10) 的失调与多种肿瘤的发生有关[1]。
与单独使用多柔比星处理的细胞相比，重塑素和多柔比星联合处理显着降低了细胞活力。 EDU 测定证实，与单独使用阿霉素处理的细胞相比，多柔比星和重塑素都能更有效地降低乳腺癌细胞增殖，这表明重塑素可减弱乳腺癌细胞中的多柔比星耐药性 (MDA-MB-231)[2]
Remodelin 每天通过胃内给药给药，持续 4 周。记录PDX模型肿瘤体积并计算TGI。因此，Remodelin 在体内显着抑制 HNSCC PDXs 的生长[3]
Remodelin治疗可抑制癌细胞的生长但不诱导细胞凋亡，即Remodelin的细胞毒性很小。 Remodelin 显着降低了 AR 阴性前列腺癌肿瘤的生长。 Remodelin 通过抑制 NAT10 的抗肿瘤作用应归功于 DNA 复制的减慢，从而减弱复制应激相关的基因组不稳定性，并最终延缓前列腺癌的进展[4]