FL118

国际站：FL118

CAS：135415-73-5

品牌：MedChemExpress (MCE)

存储条件：Powder: -20°C, 3 years; 4°C, 2 years.In solvent: -80°C, 6 months; -20°C, 1 month.

生物活性：FL118 (10,11-(Methylenedioxy)-20(S)-camptothecin), 喜树碱 (HY- 16560) 类似物，是一种有效的口服活性 survivin 抑制剂。 FL118 与癌蛋白 DDX5 (p68) 结合，使 DDX5 去磷酸化并降解。 FL118可用于癌症的研究^[1][2]。 体外：FL118 (0-200 nM; 24, 48 and 72 h ) 抑制ES-2和SK-OV₃细胞^[1]的细胞增殖。

FL118 (0-100 nM; 0 和 24 h) 抑制 ES-2 和 SK-OV₃ 细胞^[1] 的迁移。FL118 (0 -100 nM; 48 h)影响细胞珠蛋白(CYGB)的表达水平^[1]。FL118(10和100 nM; 48 h)抑制PI3K/AKT/mTOR信号通路，并影响卵巢癌细胞中波形蛋白和E-cadherin的表达水平^[1]。FL118 (0-100 nM; 6 h and 24 h)去磷酸化和降解DDX5^{[ 2]}.FL118 (0-500 nM; 24, 48, 72 h) 通过调节 DDX5 调节 survivin, McL-1, XIAP, cIAP2, c-MYc 和 mKras^[2] .FL118（0-1 μM，24 小时）对三种肿瘤细胞系（A549、MDA-MB-231 和 RM-1 细胞）显示出显着的细胞毒活性^[3] .FL118 (0-10 nM, 48 h) 增加 PARP 裂解的产生，并诱导 A549 细胞凋亡^[3].FL118 (0- 10 nM，48 小时）逮捕A549细胞主要处于G2/M期^[3]。

体内：FL118（5 和 10 mg/kg；每周口服一次，持续 20 天）抑制抗肿瘤活性^[1]。FL118（0-1.5 mg/kg，每隔一天腹腔注射一次，持续 20 天）五次）有效消除获得伊立替康或托泊替康耐药性的人类结肠和头颈肿瘤^[4]。FL118（1.5 mg/kg，静脉注射一次）表现出良好的药代动力学特征< sup>[4].FL118在雌性SCID小鼠体内的药代动力学参数^[4].

参考文献：[1]. Zhao H, et al. FL118, a novel anticancer compound, inhibits proliferation and migration of ovarian cancer cells via up-regulation of cytoglobin in vivo and in vitro[J]. Translational Cancer Research, 2017, 6(6):1294-1304.[2]. Ling X, et al. FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy. Clin Transl Med. 2022 May;12(5):e881.[3]. Wu G, et al. Synthesis of novel 10,11-methylenedioxy-camptothecin glycoside derivatives and investigation of their anti-tumor effects in vivo. RSC Adv. 2019 Apr 9;9(20):11142-11150.[4]. Ling X, et, al. FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models. Am J Transl Res. 2015 Oct 15;7(10):1765-81.