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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].
示例 | FaDu | SW620 | 等离子 |
T1/2 (hr) | 6.852 | 12.75 | 1.788 |
Tmax (hr) | 0.167 | 0.167 | 0.167 |
Cmax (ng/g, mL) | 115 | 158 | 43 |
AUC (hr*ng/g) | 413 | 842 | 82 |
AUC∞ (hr*ng/g) | 448 | 897 | 104 |
AUC% Extrap (%) | 7.74 | 6.17 | 21.7 |
Vz (g/kg) (ml/kg) | 33052 | 30742 | 36849 |
Cl (g/hr/kg) (ml/hr/kg) | 3343 | 1671 | 14287 |
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.
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