恶性胶质瘤是颅内最常见的恶性肿瘤，而有效的治疗手段有限，迫切需要新型安全高效的治疗药物。组蛋白去乙酰化酶（HDAC）与血清和糖皮质激素调节蛋白激酶1(SGK1)是防治胶质瘤的两个靶标。大黄酸具有抑制SGK1而起到抗肿瘤的作用，但活性和生物利用度偏低。为提高大黄酸的成药性，我们首次构建并合成了大黄酸与HDAC抑制剂辛二酰苯胺异羟肟酸（SAHA）拼合的新型大黄酸羟肟酸系列衍生物，并发现其中SYSUP007，与大黄酸和SAHA相比，更有效地抑制胶质瘤细胞增殖、侵袭和转移。SYSUP007能否有效治疗胶质瘤？其机制是什么？基于此，本项目拟探讨：1. SYSUP007在动物原位癌模型中对胶质瘤的杀伤作用；2. SYSUP007是否能抑制HDAC和SGK1？其抑制胶质瘤的活性是否与抑制HDAC和SGK1有关？本项目顺利完成将为确证SYSUP007为新型多靶点抗胶质瘤药物提供实验依据。

Malignant glioma is the most common type of intracranial tumor, effective treatments are limited, which proposed the urgent demand for the novel medicine for chemotherapy with high efficiency and safety. Histone deacetylase (HDAC) and serum and glucocorticoid-regulated protein kinase 1 (SGK1) are two targets for the prevention and control of gliomas. Rhein has anti-tumor effects by suppressing SGK1, but the activity and bioavailability are low. To improve the drug ability of rhein, we first constructed and synthetic a series of new Rhein-hydroxyethyl hydroxamic acid derivatives, which are combined with rhein and histone deacetylase(HDAC) inhibitor suberoylanilide hydroxamic acid(SAHA). We have found that one of the compound SYSUP007, compared with the Rhein and SAHA, was more effective in inhibiting glioma cell proliferation, invasion and metastasis in vitro. Is SYSUP007 effective in treating gliomas? What is the mechanism? Base on this, the project intends to investigate: (1)The effects of SYSUP007 on malignant glioma in vivo. (2) Whether SYSUP007 can suppress HDAC and SGK1? Whether its inhibition of glioma activity was associated with the inhibition of HDAC and SGK1? The completion of this project will provide experimental bases for confirming SYSUP007 as a new multi-targets anti-glioblastoma drug.