LY2109761
目录号 : GC12363
LY2109761是一种口服小分子双TGF-β受体（TβR）I/II激酶抑制剂（TβRI: Ki = 38nM；TβRII: Ki = 300nM）。
Cas No.:700874-71-1
Sample solution is provided at 25 µL, 10mM.
LY2109761 is an orally available, small-molecule dual TGF-β receptor (TβR) I/II kinase inhibitor (TβRI: Ki = 38nM; TβRII: Ki = 300nM) [1]. By blocking TGF-β signaling and inhibiting Smad2 phosphorylation, LY2109761 downregulates the TGF-β/Smad signaling pathway, exerting anti-proliferative and anti-invasive effects and inducing apoptosis [2-3]. LY2109761 is commonly used to treat cancer [4].
In SKOV3 cells, LY2109761 (0.5-10μM; 72h) treatment inhibited cell growth in a dose- and time-dependent manner [5]. In HepG2 cells, LY2109761 (0.1-100μM; 36h) inhibits cell proliferation by downregulating the phosphorylation of Smad-2 [6]. In AGS cells, LY2109761 (0-40μM; 2h) pretreatment inhibited cell proliferation in a dose-dependent manner after irradiation [7].
In C57BL/6 mice, LY2109761 (50mg/kg; po; twice daily for 4 weeks) attenuates radiation-induced pulmonary fibrosis in mice by reversing TGF-β and BMP-related pro-inflammatory and pro-angiogenic signaling [8]. In L3.6pl/GLT cells xenograft tumor mouse model, LY2109761 (50mg/kg; po; twice daily for 4 weeks) inhibits tumor growth and spontaneous metastasis in orthotopic xenografts in vivo [9].
References:
[1]. Sheen Y Y, Kim M J, Park S A, et al. Targeting the transforming growth factor-β signaling in cancer therapy[J]. Biomolecules & therapeutics, 2013, 21(5): 323.
[2]. Wei G, Xu Q, Liu L, et al. LY2109761 reduces TGF-β1-induced collagen production and contraction in hypertrophic scar fibroblasts[J]. Archives of Dermatological Research, 2018, 310(8): 615-623.
[3]. Chen X, Yan H, Chen Y, et al. Moderate oxidative stress promotes epithelial–mesenchymal transition in the lens epithelial cells via the TGF-β/Smad and Wnt/β-catenin pathways[J]. Molecular and cellular biochemistry, 2021, 476(3): 1631-1642.
[4]. Connolly E C, Saunier E F, Quigley D, et al. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term TβRI/II kinase inhibition with LY2109761[J]. Cancer research, 2011, 71(6): 2339-2349.
[5]. Gao Y, Shan N, Zhao C, et al. LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells[J]. International journal of clinical and experimental pathology, 2015, 8(5): 4923.
[6]. He X, Guo X, Zhang H, et al. Mechanism of action and efficacy of LY2109761, a TGF-β receptor inhibitor, targeting tumor microenvironment in liver cancer after TACE[J]. Oncotarget, 2017, 9(1): 1130.
[7]. Yang T, Huang T, Zhang D, et al. TGF-β receptor inhibitor LY2109761 enhances the radiosensitivity of gastric cancer by inactivating the TGF-β/SMAD4 signaling pathway[J]. Aging (Albany NY), 2019, 11(20): 8892.
[8]. Flechsig P, Dadrich M, Bickelhaupt S, et al. LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-β and BMP-associated proinflammatory and proangiogenic signals[J]. Clinical Cancer Research, 2012, 18(13): 3616-3627.
[9]. Melisi D, Ishiyama S, Sclabas G M, et al. LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis[J]. Molecular cancer therapeutics, 2008, 7(4): 829-840.
LY2109761是一种口服小分子双TGF-β受体（TβR）I/II激酶抑制剂（TβRI: Ki = 38nM；TβRII: Ki = 300nM） [1]。LY2109761通过阻断TGF-β信号传导和抑制Smad2磷酸化，下调TGF-β/Smad信号通路，发挥抗增殖、抗侵袭作用，并诱导细胞凋亡 [2-3]。LY2109761常用于治疗癌症 [4]。
在SKOV3细胞中，LY2109761（0.5-10μM；72h）处理以剂量和时间依赖性方式抑制细胞生长 [5]。在HepG2细胞中，LY2109761（0.1-100μM；36h）通过下调Smad-2磷酸化来抑制细胞增殖 [6]。在AGS细胞中，LY2109761（0-40μM；2h）预处理在照射后以剂量依赖性方式抑制细胞增殖 [7]。
在C57BL/6小鼠中，LY2109761（50mg/kg；po；每日两次，持续4周）通过逆转TGF-β和BMP相关的促炎和促血管生成信号，减轻小鼠放射性肺纤维化 [8]。在L3.6pl/GLT细胞异种移植肿瘤小鼠模型中，LY2109761（50mg/kg；po；每日两次，持续4周）可抑制体内原位异种移植瘤的生长和自发转移 [9]。
| Cell experiment [1]: | |
Cell lines | SKOV3 cells |
Preparation Method | SKOV3 cells were seeded at a density of 3.5 × 103 per well in 96-well microtiter culture plates. After overnight incubation, medium was removed and replaced with fresh medium containing different concentrations of LY2109761 (0.5-10μM) for 72h. On completion of incubation, viability was assessed after adding 50μL trypan blue solution (0.4% in PBS) in culture medium. After 1 to 2min, the number of dead cells, which retained the dye, was compared with the total number to calculate the percentage of viable cells. |
Reaction Conditions | 0.5-10μM; 72h |
Applications | LY2109761 treatment inhibited cell growth in a dose- and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Female C57BL/6 mice were irradiated with a single dose of 20Gy photon radiation (RT) limited to the chest. LY2109761 was administered by oral gavage twice daily for 4 weeks at a dose of 50mg/kg body weight dissolved in 1% carboxymethylcellulose sodium (CMS) USP. Mice were randomly distributed to 6 groups group 1 (LY2109761, RT), LY2109761 treatment started 4 weeks before RT; group 2 ( LY2109761, RT), LY2109761 treatment started 2 weeks before RT and continued for 2 weeks after RT; group 3 (RT, LY2109761), LY210976 started 1 day after RT; group 4 (LY2109761), LY2109761 was given over 4 weeks without RT; group 5 (RT), only RT; group 6 (control), only CMS. |
Dosage form | 50mg/kg; po; twice daily for 4 weeks |
Applications | LY2109761 attenuates radiation-induced pulmonary fibrosis in mice by reversing TGF-β and BMP-related pro-inflammatory and pro-angiogenic signaling. |
References: | |
| Cas No. | 700874-71-1 | SDF | |
| 化学名 | 4-[2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl]oxyethyl]morpholine | ||
| Canonical SMILES | C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6 | ||
| 分子式 | C26H27N5O2 | 分子量 | 441.52 |
| 溶解度 | ≥ 22.1mg/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 | 2.2649 mL | 11.3245 mL | 22.649 mL |
| 5 mM | 0.453 mL | 2.2649 mL | 4.5298 mL |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2649 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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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