158440-71-2

• 常用中文名：(-)-Irofulven
• 常用英文名：(-)-Irofulven
• CAS号：158440-71-2
• 分子式：C₁₅H₁₈O₃
• 分子量：246.30200
• 相关类别： 信号通路 细胞凋亡 细胞凋亡
• 发布时间：2017-06-14 12:52:33
• 更新时间：2024-01-09 12:04:24
• (-)-Irofulven(MGI 114),一种伊卢定S类似物,是一种DNA烷基化剂。(-)-Irofulven抑制DNA复制,诱导肿瘤细胞凋亡,并具有强大的抗肿瘤活性[1][2]。

名称

• 英文名: (5'R)-5'-hydroxy-1'-(hydroxymethyl)-2',5',7'-trimethylspiro[cyclopropane-1,6'-indene]-4'-one
• 英文别名: HMAF; Spiro(cyclopropane-1,5'(5H)-inden)-7'(6'H)-one,6'-hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethyl-,(R); [14C]-Irofulven; 6-hydroxymethylacylfulvene; (-)-irofulven; Acylfulvene,6-(hydroxymethyl); MGI 114

物化性质

• 密度: 1.28g/cm3
• 沸点: 501ºC at 760 mmHg
• 分子式: C₁₅H₁₈O₃
• 分子量: 246.30200
• 闪点: 270.9ºC
• 精确质量: 246.12600
• PSA: 57.53000
• LogP: 1.66560
• 蒸汽压: 3.9E-12mmHg at 25°C
• 折射率: 1.617
• 储存条件: -20°C

生物活性

• 描述: (-)-Irofulven(MGI 114),一种伊卢定S类似物,是一种DNA烷基化剂。(-)-Irofulven抑制DNA复制,诱导肿瘤细胞凋亡,并具有强大的抗肿瘤活性[1][2]。
• 相关类别:
  信号通路 >> 细胞凋亡 >> 细胞凋亡
  研究领域 >> 癌症
  信号通路 >> 细胞周期/DNA损伤 >> DNA烷基化剂/交联剂
• 体外研究: (-)-Irofulven(2.8μM；1小时)诱导p53依赖性细胞周期阻滞[1]。(-)-Irofulven(0.8μM、0.9μM和2.8μM；1小时)诱导CHK2激活与细胞中的p53状态有关[1]。(-)-Irofulven抑制DNA复制并诱导染色体畸变(断裂和放射状)[1]。细胞周期分析[1]细胞系：A2780、CAOV3和HCT116细胞浓度：2.8μM孵育时间：1小时结果：p53野生型细胞主要阻滞于G1/S期,而p53突变或p53缺失细胞则阻滞于S期和G2/M期。Western Blot分析[1]细胞系：A2780、CAOV3和HCT116细胞浓度：0.8μM、0.9μM和2.8μM培养时间：1小时结果：诱导细胞内CHK2激酶的Thr 68磷酸化。
• 体内研究: (-)-Irofulven(第1-5天和第8-12天为7 mg/kg；i.p.)可显著提高荷瘤小鼠的中位生存率[2]。动物模型：雄性和雌性无胸腺BALB/c小鼠(nu/nu基因型,6周龄或以上)注射人类多形性胶质母细胞瘤[2]。剂量：7mg/kg给药：腹腔注射；在第1-5天和第8-12天,结果：对所有肿瘤细胞株都有效。
• 参考文献:

  [1]. Yutian Wang, et al. Irofulven induces replication-dependent CHK2 activation related to p53 status. Biochem Pharmacol. 2007 Feb 15;73(4):469-80.

  [2]. H S Friedman, et al. Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice. Cancer Chemother Pharmacol. 2001 Nov;48(5):413-6.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : WH0204487 CHEMICAL NAME : Spiro(cyclopropane-1,5'(5H)-inden)-7'(6'H)-one, 6'-hydroxy-3'-(hydroxymethyl)-2',4',6'- trimethyl-, (R)- CAS REGISTRY NUMBER : 158440-71-2 LAST UPDATED : 199712 DATA ITEMS CITED : 4 MOLECULAR FORMULA : C15-H18-O3 MOLECULAR WEIGHT : 246.33 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >6610 ug/kg TOXIC EFFECTS : Cardiac - other changes Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified) REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2 mg/kg TOXIC EFFECTS : Blood - thrombocytopenia Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified) REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 20339 ug/kg/5D-I TOXIC EFFECTS : Cardiac - other changes Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified) REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 3 mg/kg/5D-I TOXIC EFFECTS : Blood - thrombocytopenia Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified) REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997

合成路线

50-00-0 33781-60-1 ~75% 158440-71-2

文献：McMorris, Trevor C.; Hu, Yi; Yu, Jian; Kelner, Michael J. Chemical Communications, 1997 , # 3 p. 315 - 316

1149-99-1 ~% 158440-71-2

文献：Journal of Labelled Compounds and Radiopharmaceuticals, , vol. 41, # 4 p. 279 - 285

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