Voreloxin | 1393-48-2

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Voreloxin
• 英文别名: N-[3-[(3-amino-3-oxoprop-1-en-2-yl)amino]-3-oxoprop-1-en-2-yl]-2-[(1R,8S,11Z,18S,25S,26R,37S,40S,46S,53S,59S)-37-[(2S)-butan-2-yl]-18-[(2S,3R)-2,3-dihydroxybutan-2-yl]-11-ethylidene-59-hydroxy-8-[(1R)-1-hydroxyethyl]-31-[(1S)-1-hydroxyethyl]-26,40,46-trimethyl-43-methylidene-6,9,16,23,28,38,41,44,47-nonaoxo-27-oxa-3,13,20,56-tetrathia-7,10,17,24,36,39,42,45,48,52,58,61,62,63,64-pentadecazanonacyclo[23.23.9.329,35.12,5.112,15.119,22.154,57.01,53.032,60]tetrahexaconta-2(64),4,12(63),19(62),21,29(61),30,32(60),33,51,54,57-dodecaen-51-yl]-1,3-thiazole-4-carboxamide
• CAS: 1393-48-2
• 化学式: C₇₂H₈₅N₁₉O₁₈S₅
• 分子量: 1664.9
• InChiKey: NSFFHOGKXHRQEW-WGQXSCKOSA-N

物化性质

• 熔点：
  248-257°C (dec.)
• 比旋光度：
  D23 -98.5° (glacial acetic acid); -61° (dioxane); -20° (pyridine)
• 密度：
  1.0824 (rough estimate)
• 溶解度：
  溶于DMSO或氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  114
• 可旋转键数：
  12
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  701
• 氢给体数：
  17
• 氢受体数：
  31

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S24/25
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  29419090

制备方法与用途

生物活性

Thiostrepton 是一种抗生素，可选择性抑制 FOXM1。FOXM1 与 YAP/TEAD 复合物结合。YAP/TEAD/FOXM1 复合物在控制细胞周期的基因调控区域结合可能会影响细胞增殖。

体外研究

Thiostrepton（0.01-1000 μM，48 小时）抑制了 A2780 和 HEC-1A 细胞的存活率。具体结果如下：

细胞系	浓度 (μM)	孵育时间 (小时)	IC₅₀ (μM)
A2780	0.01, 0.1, 1, 10, 100, 1000	48	1.10
HEC-1A	0.01, 0.1, 1, 10, 100, 1000	48	2.22

体内研究

Thiostrepton（腹腔注射，剂量为 17 mg/kg）减少了 Ewing 肉瘤 (EWS) 细胞的肿瘤发生率。与对照组小鼠相比，接受 Thiostrepton 治疗的小鼠其肿瘤体积仅增加了约 1.7 倍，相对于对照组而言，减少幅度约为 3.5 倍。

动物模型	细胞系	剂量 (mg/kg)	给药方式	结果
裸鼠 (BALB/c nu/nu)	A4573	17	腹腔注射	Thiostrepton 治疗抑制了 EWS 细胞来源的肿瘤生长。

文献信息

• REACTIVITY-BASED SCREENING FOR NATURAL PRODUCT DISCOVERY
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US20170227545A1

  公开（公告）日：2017-08-10

  A method of identifying a natural product comprising NP—[X] n is provided. The method includes several steps. The first step includes selecting an organism having a biosynthetic pathway for producing the natural product comprising NP—[X] n using a bioinformatics algorithm. The second step includes preparing a sample suspected to contain NP—[X] n including a complex cellular metabolite mixture from an organism. The third step includes reacting the sample suspected to contain NP—[X] n with reactivity probe Y according to Scheme I: Scheme I. NP—[X] n represents a natural product NP having a chemical moiety X that is susceptible to chemical modification by reactivity probe Y to form at least one product adduct NP—[X] n-m [Z] n in which chemical moiety X reacts with reactivity probe Y to form adduct Z, wherein n ranges from 1 to about 10 and m is at least 1 and m≦n. The fourth step includes optionally dereplicating the product collection of at least one known labeled metabolite to provide a depleted product collection including at least one unknown labeled metabolite. The fifth step includes determining the structure of the at least one unknown labeled metabolite, thereby identifying the natural product comprising NP—[X] n .