LY364947
(Synonyms: HTS466284) 目录号 : GC11604
Inhibitor of TGF-β type-1 receptors
Cas No.:396129-53-6
Sample solution is provided at 25 µL, 10mM.
The multifunctional cytokine transforming growth factor-β (TGF-β) is a member of a large family of growth factors involved in the regulation of a diverse array of biological processes including cell growth and differentiation, matrix modulation, and embryonic development. LY364947 is a inhibitor of the transforming growth factor-β type I receptor kinase domain.
In vitro: LY364947 was quickly identified as a potent inhibitor (IC50= 51 nM) and was chosen as a platform for SAR development. Compounds were further evaluated as inhibitors of TGF-β-dependent luciferase production in mink lung cells (p3TP Lux) and growth in mouse fibroblasts (NIH 3T3) [1].
In vivo: In a rat model of NMDA-induced retinal degeneration, simultaneous injection of NMDA and the TGF-β inhibitor LY364947 slightly but significantly attenuated the reduction in number of cells in the ganglion cell layer and almost completely prevented the enhancement of capillary degeneration. [3].
Clinical trial: Up to now, LY364947 is still in the preclinical development stage.
Reference:
[1] Sawyer JS, Anderson BD, Beight DW, Campbell RM, Jones ML, Herron DK, Lampe JW, McCowan JR, McMillen WT, Mort N, Parsons S, Smith EC, Vieth M, Weir LC, Yan L, Zhang F, Yingling JM. Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. J Med Chem. 2003 Sep 11;46(19):3953-6.
[2] Ueda K, Nakahara T, Mori A, Sakamoto K, Ishii K. Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration. Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93.
| Kinase experiment [1]: | |
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Filter-binding assay |
The IC50 values of LY364947 at different enzyme concentrations were determined by the filter-binding assay. Typically, 40 μL reactions in 50 mM HEPES at pH 7.5, 1 mM NaF, 200 μM pKSmad3(-3) and 50 mM ATP containing a titration of each inhibitor with concentrations of 1600, 800, 400, 200, 100, 50, 25, and 0 nM were incubated at 30 °C for 30 mins. The IC50 values were calculated using a nonlinear regression method with GraphPad Prism software. The binding type was determined by plotting the correlation between enzyme concentrations and IC50 values. |
| Cell experiment [2]: | |
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Cell lines |
HOXB9-MCF10A cells |
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Preparation method |
The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
10 μM; 24 hrs |
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Applications |
In HOXB9-MCF10A cells, LY364947 suppressed Smad2 phosphorylation by inhibiting TGF-β activation, meanwhile, without affecting the expression of TGF-β1 and TGF-β2. Besides, LY364947 induced epithelial morphological changes, with re-expression of E-cadherin as well as suppression of fibronectin and vimentin. In addition, LY364947 reduced migration and invasiveness of HOXB9-MCF10A cells. |
| Animal experiment [3]: | |
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Animal models |
A rat model of NMDA-induced retinal degeneration |
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Dosage form |
50 nM; 5μL; intravitreal injection |
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Applications |
In a rat model of NMDA-induced retinal degeneration, LY364947 significantly suppressed cell loss in the ganglion cell layer induced by NMDA. Besides, LY364947 markedly prevent vascular damage in the injured retina caused by NMDA. In addition, co-treatment with NMDA and LY364947 did not cause any morphological change of NG2-positive pericytes. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Peng SB, Yan L, Xia X, Watkins SA, Brooks HB, Beight D, Herron DK, Jones ML, Lampe JW, McMillen WT, Mort N, Sawyer JS, Yingling JM. Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry. 2005 Feb 22;44(7):2293-304. [2]. Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco Md, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1100-5. [3]. Ueda K, Nakahara T, Mori A, Sakamoto K, Ishii K. Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration. Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93. |
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| Cas No. | 396129-53-6 | SDF | |
| 别名 | HTS466284 | ||
| 化学名 | 4-(5-pyridin-2-yl-1H-pyrazol-4-yl)quinoline | ||
| Canonical SMILES | C1=CC=C2C(=C1)C(=CC=N2)C3=C(NN=C3)C4=CC=CC=N4 | ||
| 分子式 | C17H12N4 | 分子量 | 272.3 |
| 溶解度 | ≥ 24.4mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6724 mL | 18.3621 mL | 36.7242 mL |
| 5 mM | 0.7345 mL | 3.6724 mL | 7.3448 mL |
| 10 mM | 0.3672 mL | 1.8362 mL | 3.6724 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet