GSK1838705A是一种小分子激酶抑制剂，可靶向胰岛素样生长因子1受体（IGF-1R）和胰岛素受体，其IC₅₀分别为2.0nM和1.6nM。
Cas No.:1116235-97-2
Sample solution is provided at 25 µL, 10mM.
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GSK1838705A is a small-molecule kinase inhibitor that targets Insulin-like Growth Factor 1 Receptor (IGF-1R) and the insulin receptor, with IC₅₀ values of 2.0nM and 1.6nM, respectively. IGF-1R and the insulin receptor are transmembrane receptors involved in growth and metabolic signaling pathways. GSK1838705A also inhibits anaplastic lymphoma kinase (ALK) with an IC₅₀ of 0.5nM. Through inhibition of ALK, GSK1838705A suppresses the growth of tumors such as anaplastic large-cell lymphoma, neuroblastoma, and a subset of non–small cell lung cancers, and is considered a promising antitumor agent[1].
In vitro, GSK1838705A exhibited EC₅₀ values ranging from 0.20nM to above 8μM in cell lines derived from solid and hematologic tumors, and below 1μM in most multiple myeloma and Ewing’s sarcoma cell lines. In NIH-3T3/LISN, NIH-3T3-hIR, and MCF-7 cells, treatment with 0.01-3μM GSK1838705A for 4h inhibited IGF-I- or insulin-induced phosphorylation of IGF-1R and IR in a concentration-dependent manner, accompanied by a parallel decrease in phosphorylated AKT, IRS-1, and ERK[1].
In vivo, in NIH-3T3/LISN, COLO 205, HT29, and BxPC3 xenograft-bearing mice, oral administration of GSK1838705A (10, 30, or 60mg/kg/day) for 21 days inhibited tumor growth in a dose-dependent manner. Tumor growth inhibition reached 17%, 45%, and 77% in NIH-3T3/LISN tumors and 34%, 80%, and 78% in COLO 205 tumors at 10, 30, and 60mg/kg, respectively. In HT29 xenografts, 60mg/kg GSK1838705A resulted in 42% tumor growth inhibition, while in BxPC3 xenografts, inhibition reached 56% and 60% at 30 and 60mg/kg, respectively[1].
References:
[1] Sabbatini P, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.
GSK1838705A是一种小分子激酶抑制剂，可靶向胰岛素样生长因子1受体（IGF-1R）和胰岛素受体，其IC₅₀分别为2.0nM和1.6nM。IGF-1R和胰岛素受体均为跨膜受体，参与生长和代谢信号通路。GSK1838705A还可抑制间变性淋巴瘤激酶（ALK），其IC₅₀为0.5nM。通过抑制ALK，GSK1838705A可抑制间变性大细胞淋巴瘤、神经母细胞瘤以及部分非小细胞肺癌等肿瘤的生长，并被认为是一种具有前景的抗肿瘤药物[1]。
体外实验中，GSK1838705A在来源于实体瘤和血液肿瘤的细胞系中，其EC₅₀范围为0.20nM到大于8μM；而在大多数多发性骨髓瘤和尤文肉瘤细胞系中，其EC₅₀低于1μM。在NIH-3T3/LISN，NIH-3T3-hIR和MCF-7细胞中，0.01-3μM GSK1838705A处理4h可剂量依赖性抑制IGF-I或胰岛素诱导的IGF-1R和IR的磷酸化，同时伴随AKT，IRS-1和ERK磷酸化水平的同步下降[1]。
体内实验中，在NIH-3T3/LISN、COLO 205、HT29和BxPC3异种移植瘤小鼠模型中，口服给予GSK1838705A（10、30或60mg/kg/day）连续21天，可剂量依赖性抑制肿瘤生长。在NIH-3T3/LISN模型中，10、30和60mg/kg的肿瘤生长抑制率分别为17%、45%和77%；在COLO 205模型中分别为34%、80%和78%。在HT29异种移植瘤中，60mg/kg GSK1838705A的肿瘤生长抑制率为42%；在BxPC3模型中，30和60mg/kg的抑制率分别为56%和60%[1]。
| Cell experiment [1]: | |
Cell lines | NIH-3T3/LISN, NIH-3T3-hIR, and MCF-7 cell lines |
Preparation Method | NIH-3T3/LISN, NIH-3T3-hIR, and MCF-7 cell lines were plated in normal growth medium. After 24h, the medium was replaced with serum-free medium, and DMSO (0.2%) or GSK1838705A was added to the cells. Four hours later, cells were stimulated with 30ng/mL IGF-I or 3μg/mL insulin for 15min. Whole-cell lysates were resolved by SDS-PAGE and analyzed by Western blotting. |
Reaction Conditions | 0.01-3μM; 4h |
Applications | GSK1838705A inhibited IGF-I or insulin-induced phosphorylation of IGF-IR and IR in a concentration-dependent manner, with a parallel decrease in phosphorylated AKT, IRS-1, and ERK. |
| Animal experiment [1]: | |
Animal models | NIH-3T3/LISN tumor, COLO 205 tumor, HT29 xenograft and BxPC3 xenografts–bearing mice (8 to 12-week-old female nu/nu CD-1 mice) |
Preparation Method | GSK1838705A was formulated in 20% sulfobutyl ether β-cyclodextrin. Tumor xenograft-bearing nude mice were treated with vehicle or GSK1838705A (10, 30, or 60mg/kg) by oral administration once daily for 21 days. Tumor size was measured twice weekly. |
Dosage form | 10, 30 and 60mg/kg/d; 21d; p.o. |
Applications | Treatment of NIH-3T3/LISN tumor–bearing mice with GSK1838705A at 10, 30, and 60mg/kg once daily resulted in 17%, 45%, and 77% tumor growth inhibition, respectively, at the end of the treatment period. Treatment of COLO 205 tumor–bearing mice with GSK1838705A at 10, 30, and 60mg/kg once daily resulted in 34%, 80%, and 78% inhibition of tumor growth, respectively. In HT29 xenograft–bearing mice, 60mg/kg GSK1838705A caused a 42% tumor growth inhibition relative to vehicle-treated controls at the end of the treatment period. In animals bearing BxPC3 xenografts, tumor growth inhibition at the end of the treatment period was 56% and 60% with doses of 30 and 60mg/kg, respectively. |
References: | |
| Cas No. | 1116235-97-2 | SDF | |
| 化学名 | 2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide | ||
| Canonical SMILES | CNC(=O)C1=C(C=CC=C1F)NC2=NC(=NC3=C2C=CN3)NC4=C(C=C5CCN(C5=C4)C(=O)CN(C)C)OC | ||
| 分子式 | C27H29FN8O3 | 分子量 | 532.57 |
| 溶解度 | ≥ 26.65mg/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 | 1.8777 mL | 9.3884 mL | 18.7769 mL |
| 5 mM | 375.5 μL | 1.8777 mL | 3.7554 mL |
| 10 mM | 187.8 μL | 938.8 μL | 1.8777 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。
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