TAK-441

• 常用名: TAK-441
• 英文名: TAK-441
• CAS号: 1186231-83-3
• 分子量: 576.564
• 密度: 1.4±0.1 g/cm3
• 沸点: 761.6±60.0 °C at 760 mmHg
• 分子式: C₂₈H₃₁F₃N₄O₆
• 熔点: N/A
• 闪点: 414.4±32.9 °C

TAK-441用途

TAK-441(化合物11d)是一种高效的口服刺猬(Hh)信号抑制剂,IC50值为4.4nM。TAK-441(化合物11d)在实体瘤中具有较强的抗肿瘤活性[1]。

TAK-441名称

• 英文名: 6-Ethyl-N-(1-glycoloyl-4-piperidinyl)-1-methyl-4-oxo-5-(2-oxo-2-p henylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2- c]pyridine-2-carboxamide

TAK-441生物活性

• 描述: TAK-441(化合物11d)是一种高效的口服刺猬(Hh)信号抑制剂,IC50值为4.4nM。TAK-441(化合物11d)在实体瘤中具有较强的抗肿瘤活性[1]。
• 相关类别:
  研究领域 >> 癌症
  信号通路 >> 干细胞及 Wnt 通路 >> Hedgehog
• 靶点实验:

  IC50: 4.4 nM (Gli-luc reporter)[1]

• 体外研究: TAK-441(化合物11d)在Gli-luc报告中具有强活性,IC50值为4.4nM,溶解性好。TAK-441在肿瘤和皮肤中抑制Gli1 mRNA,IC50值分别为0.0457和0.113mg/ml。TAK-441不影响雄激素戒断诱导的Shh上调或LNCaP细胞的活力。TAK-441通过破坏与肿瘤基质的旁分泌Hh信号,导致LNCaP异种移植物延迟去势抗性进展[1][2][3]。细胞活力测定[1]细胞系：NIH3T3/Gli-luc细胞浓度：0.03–1000 nM孵育时间：48 h结果：显示出可接受的溶解度和有效的Hh抑制活性。细胞存活率测定[3]细胞系：LNCaP细胞浓度：0.5-500 nM孵育时间：48-72 h结果：在雄激素剥夺条件下,不影响LNCaP细胞体外存活率Shh的上调。Western Blot分析[3]细胞系：LNCaP、C4-2、DU145和PC3细胞浓度：孵育时间：结果：反映雄激素反应性PCa,在LNCaP和C4-3细胞中表达Shh和Dhh,并反映DU145和PC3细胞中CRPC的限制性Shh表达。
• 参考文献:

  [1]. Tomohiro Ohashi, et al. Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility. Bioorg Med Chem. 2012 Sep 15;20(18):5507-17.

  [2]. Akifumi Kogame, et al. Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK-441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice. Drug Metab Dispos

  [3]. Naokazu Ibuki, et al. TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. Int J Cancer. 2013 Oct 15;133(8):1955-66.

TAK-441物理化学性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 761.6±60.0 °C at 760 mmHg
• 分子式: C₂₈H₃₁F₃N₄O₆
• 分子量: 576.564
• 闪点: 414.4±32.9 °C
• 精确质量: 576.219543
• PSA: 126.36000
• LogP: 2.64
• 蒸汽压: 0.0±2.7 mmHg at 25°C
• 折射率: 1.606

TAK-441靶点实验

查看更多实验

实验名称：Cellular viability qHTS for adrenocortical cancer (ACC) cell line SW-13 来源：NCGC 靶标：N/A External Id：ACC-ATC-p1-SW13-72hr

实验名称：Cellular viability qHTS for adrenocortical cancer (ACC) cell line NCI-H295R 来源：NCGC 靶标：N/A External Id：ACC-ATC-p1-H295R-72hr

实验名称：Cytotoxicity counterscreen for inhibitors of SARS-CoV-2 cell entry 来源：NCGC 靶标：N/A External Id：TRND-SARS-CoV-2-cytotox-48hr

实验名称：Primary qHTS to identify inhibitors of SARS-CoV-2 cell entry 来源：NCGC External Id：TRND-SARS-CoV-2-PP

实验名称：In vivo inhibition of Gli1 mRNA expression in mouse bearing human PAN-04 cells assess... 来源：ChEMBL 靶标：N/A External Id：CHEMBL3594906

实验名称：AUC (0 to 8 hrs) in non-fasted mouse at 10 mg/kg, po cassette dosing by LC/MS/MS anal... 来源：ChEMBL 靶标：Mus musculus External Id：CHEMBL3594907

实验名称：Primary qHTS Assay for Inhibitors of Recombinant Selenoprotein Glutathione Peroxidase... 来源：NCGC External Id：GPx1-biochemical-p4-p7

实验名称：Diffuse intrinsic pontine glioma (SU-DIPG-XVII) cell line screen of MIPE5.0 library: ... 来源：15316 靶标：N/A External Id：s-dipg-DIPG17_CTG48h_mipe5_0-1

实验名称：qHTS drug screen for cell cycle checkpoint inhibitors in PARPi-resistant BRCA-mutant ... 来源：NCGC External Id：FGL-PARP_PEO-CTG96h-MIPE5.0-p1

实验名称：Oral bioavailability in dog at 10 mg/kg 来源：ChEMBL 靶标：Canis lupus familiaris External Id：CHEMBL2213619

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TAK-441英文别名

• s-Triazine,4,6-bis(isopropylamino)-2-ethyl
• 6-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
• 2-Ethyl-4,6-bis(iso-propylamino)-s-triazine
• 2-ethyl-4,6-bis(isopropylamino)-1,3,5-triazine
• [11] 6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
• 6-ethyl-N,N'-diisopropyl-[1,3,5]triazine-2,4-diamine
• 4,6-Bis(isopropylamino)-2-ethyl-s-triazine
• 6-Ethyl-N-(1-glycoloyl-4-piperidinyl)-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
• 6-ethyl-N,N'-di(propan-2-yl)-1,3,5-triazine-2,4-diamine