2018年5月1日 · Leptomycin B (LMB; Elactocin or CI 940), derived from Streptomyces sp., was the first and most widely studied nuclear export inhibitor (NEI) before SINE compounds. 10 An irreversible inhibitor of XPO1, LMB was found to have highly potent antitumor activity in various cell lines and murine xenograft models 39, 40; however, further development ...

2015年11月5日 · Here we demonstrate for the first time that targeted inhibition of nuclear exporter protein exportin 1 (XPO1) also known as chromosome maintenance region 1 (CRM1) by Selective Inhibitor of...

核输出蛋白1 （exportin 1, XPO1）又称染色体区域稳定蛋白1，通过调节从细胞核到细胞质的一系列“货物”（包括蛋白质和几种RNA）的输出，在维持细胞内稳态中起着至关重要的作用。 这种蛋白的失调在各种实体和血液恶性肿瘤的发展中起着关键作用。 此外， XPO1与多种标准的治疗方法 （包括化疗和靶向治疗） 的耐药性有关，使其成为 新型癌症疗法的一个有吸引力的靶点。 多年来，一些选择性的核输出蛋白抑制剂已被开发出来。 然而，只有 selinexor 已经过临床验证。 来 …

2022年5月5日 · LMB is the first-generation and most well-known inhibitor of XPO1. However, the high toxicity of LMB resulted from the permanent inhibition of nuclear export led to barely any clinical benefit [25, 26].

Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of...

2012年11月11日 · Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby inhibiting nuclear export of cargo proteins. The clinical relevance of SINEs was explored in chronic lymphocytic leukemia (CLL), a disease associated with recurrent XPO1 mutations.

2022年1月31日 · Exportin 1 (XPO1) is a karyopherin-β responsible for nuclear export of at least several hundred proteins and multiple types of RNA molecules. In this short review we consider the role of XPO1 in pathogenesis of cancer and clinical applications of XPO1 inhibitors.

2014年7月17日 · Orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to and inhibit the function of XPO1 have been recently developed. The aim of this study was to investigate the efficacy of the clinical staged, orally available, SINE compound, KPT-330 in hepatocellular carcinoma (HCC).

2019年2月3日 · Chromosome region maintenance 1 (CRM1), better known as exportin 1 (XPO1), is the protein transporter responsible for the nucleo-cytoplasmic shuttling of most of the tumor suppressor proteins (TSP) and growth regulatory factors. XPO1 is also upregulated in many malignancies and associated with a poor prognosis.

2016年5月20日 · We designed a new generation SINE compound, KPT-8602, with a similar mechanism of XPO1 inhibition and potency but considerably improved tolerability. Efficacy of KPT-8602 was evaluated in...