Zheng Shilong, Guo Shanchun, Zhong Qiu, Zhang Changde, Liu Jiawang, Yang Lin, Zhang Qiang, Wang Guangdi
RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, Louisiana 70125, United States.
Chongqing Medical and Pharmaceutical College, No. 82, Middle Rd, University Town, Chongqing 401331, China.
ACS Med Chem Lett. 2018 Jan 8;9(2):149-154. doi: 10.1021/acsmedchemlett.7b00504. eCollection 2018 Feb 8.
Despite promising therapeutic utilities for treatment of hematological malignancies, histone deacetylase inhibitor (HDACi) drugs have not proven as effective in the treatment of solid tumors. To expand the clinical indications of HDACi drugs, we developed novel boron-containing prodrugs of belinostat (), one of which efficiently releases active through a cascade of reactions in cell culture and demonstrates activities comparable to against a panel of cancer cell lines. Importantly, prodrug is more efficacious than belinostat in vivo, not only inhibiting the growth of tumor but also reducing tumor volumes in an MCF-7 xenograft tumor model owing to its superior biocompatibility, which suggests its clinical potential in the treatment of solid tumors.
尽管组蛋白去乙酰化酶抑制剂（HDACi）药物在治疗血液系统恶性肿瘤方面具有潜在的治疗效用，但尚未证明其在实体瘤治疗中同样有效。为了扩大HDACi药物的临床适应症，我们研发了新型的贝利司他含硼前药，其中一种前药在细胞培养中通过一系列反应有效释放出活性成分，并且在一组癌细胞系中表现出与贝利司他相当的活性。重要的是，前药在体内比贝利司他更有效，不仅能抑制肿瘤生长，还能在MCF-7异种移植肿瘤模型中减小肿瘤体积，这归因于其卓越的生物相容性，表明其在实体瘤治疗中的临床潜力。
