1. Stem Cell/Wnt Apoptosis Epigenetics
  2. Hedgehog Apoptosis DNA Methyltransferase
  3. Hedgehog IN-11

Hedgehog IN-11 是一种口服有效的 Hedgehog 抑制剂。Hedgehog IN-11 通过 Hedgehog 通路下调 O6-甲基鸟嘌呤-脱氧核糖核苷酸甲基转移酶 (MGMT) 的表达,从而降低 Temozolomide (TMZ) (HY-17364) 的耐药性。Hedgehog IN-11 能显著抑制耐 TMZ 的胶质母细胞瘤细胞迁移和侵袭,并诱导细胞凋亡 (apoptosis)。Hedgehog IN-11 经计算机模拟预测具有良好的血脑屏障穿透性。Hedgehog IN-11 可用于胶质母细胞瘤 (GBM) 的研究。

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Hedgehog IN-11

Hedgehog IN-11 Chemical Structure

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查看 DNA Methyltransferase 亚型特异性产品:

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

Hedgehog IN-11 is an orally active Hedgehog inhibitor. Hedgehog IN-11 downregulates the expression of O6-methylguanine-DNA methyltransferase (MGMT) to impair the Temozolomide (TMZ) (HY-17364) resistance by inhibiting the Hedgehog pathway. Hedgehog IN-11 shows improved inhibition of cell migration and invasion, and induced cell apoptosis in TMZ-resistant GBM cell lines. Hedgehog IN-11 is predicted by computer simulation to have good blood-brain barrier penetration. Hedgehog IN-11 can be used for the study of glioblastoma (GBM)[1].

IC50 & Target[1]

MGMT

 

体外研究
(In Vitro)

Hedgehog IN-11 (Compound 10c2) (72 h) 对 U87MG、T98G、U343/TMZ 和 U251/TMZ 细胞具有抑制增殖的作用,其 IC50 值分别为 0.27、0.70、0.35 和 0.65 nM,对 GES-1 细胞的细胞毒性较低,其半数细胞毒性浓度 (CC50) 为 1.12 nM[1]
Hedgehog IN-11 (0.05-5 nM, 24 h-12 d) 抑制 T98G 细胞的集落形成、迁移和侵袭[1]
Hedgehog IN-11 (0.05-50 nM, 12 h) 诱导 T98G 细胞凋亡,并通过抑制 Hedgehog 信号通路抑制 MGMT 的表达[1]

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Migration Assay [1]

Cell Line: T98G cells
Concentration: 0.05, 0.5 and 5 nM
Incubation Time: 24 h
Result: Significantly reduced the migration.

Cell Invasion Assay[1]

Cell Line: T98G cells
Concentration: 0.05, 0.5 and 5 nM
Incubation Time: 24 h
Result: Obviously inhibited the invasion.

Apoptosis Analysis[1]

Cell Line: T98G cells
Concentration: 0.05, 0.5 and 5 nM
Incubation Time: 12 h
Result: Resulted in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive DNA strand breaking.

Western Blot Analysis[1]

Cell Line: T98G cells
Concentration: 0.05, 0.5 and 5 nM
Incubation Time: 24 h
Result: Resulted in elevated expression of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP) and phosphorylated H2AX (γ-H2AX) in a dose-dependent manner.
Demonstrated dose-dependent inhibition of Gli1 and MGMT.
体内研究
(In Vivo)

Hedgehog IN-11 (Compound 10c2) (6-12 mg/kg, p.o., 共 13 天) 在小鼠体内对耐 TMZ 的胶质母细胞瘤显示出良好的疗效,并且能够有效增强 TMZ 的治疗效果[1]

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: T98G xenograft model established in NCG mice (female, 18-20 g)[1]
Dosage: 6 mg/kg (with or without TMZ) and 12 mg/kg alone
Administration: Oral administration (p.o.), for 13 days
Result: Significantly inhibited tumor growth with the tumor growth inhibition (TGI) rates of 60 % for low-dose, 69.7 % for high-dose in monotherapy.
Yields better results with TGI of 76.6% in the combined treatment.
分子量

602.60

Formula

C33H29F3N4O4

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.

纯度 & 产品资料
参考文献
  • 摩尔计算器

  • 稀释计算器

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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产品名称:
Hedgehog IN-11
目录号:
HY-175299
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