OSI-027
(Synonyms: 反式-4-[4-氨基-5-(7-甲氧基-1H-吲哚-2-基)咪唑并[5,1-F][1,2,4]三嗪-7-基]环己烷羧酸,ASP7486) 目录号 : GC14071
OSI-027是一种选择性小分子口服抑制剂，可同时抑制mTORC1和mTORC2的激酶活性，IC50值分别为22nM和65nM。
Cas No.:936890-98-1
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
OSI-027 is a selective small molecule oral inhibitor that can simultaneously inhibit the kinase activities of mTORC1 and mTORC2, with IC50 values of 22nM and 65nM, respectively[1]. OSI-027 blocks mTORC1/2 activation, and results in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4)[2]. OSI-027 has been widely used as an anti-cancer agent to inhibit tumor growth in animal models of xenografts[3].
In vitro, OSI-027 treatment for 24 hours significantly reduced the cell viability of Panc-1, BxPC-3 and CFPAC-1 cells, with IC50 values were 21.57μM, 8.360μM and 13.72μM, respectively[4]. Treatment with 10μM OSI-027 for 48 hours induced apoptosis in HCT116 and SW620 cells, significantly up-regulating the protein levels of Bax, Bim, cleaved-caspase 3, FOXO3a and PUMA in colon cancer cells[5]. Treatment with 4μM OSI-027 for 48 hours induced cell cycle arrest in Hep-3B cells and inhibited the phosphorylation of mTORC1 substrates in Hep-3B cells, including 4E-BP1 (Thr37/46) and p70S6K (Thr389)[6].
In vivo, OSI-027 treatment via intraperitoneal injection at a dose of 0.5mg/kg (three times a week) for two consecutive weeks significantly reduced inflammation in the alveolar cavities and alveolar septa, and alleviated lung injury and fibrosis in the models of lung injury in juvenile rats caused by hyperoxia[7]. Daily intraperitoneal injection of 10mg/kg dose of OSI-027 and 5mg/kg dose of SB202190 for 12 days can significantly inhibit tumor growth in mice with xenografted SW620 tumors and induce apoptosis of tumor cells[8].
References:
[1] Gokhale P C, Bhagwat S V, Crew A P, et al. OSI-027, a selective dual mTORC1/TORC2 kinase inhibitor displays broad spectrum anti-tumor activity in preclinical models of human cancer[J]. Cancer Research, 2010, 70(8_Supplement): 4486-4486.
[2] Xu E, Zhu H, Wang F, et al. OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction[J]. Current Molecular Medicine, 2021, 21(10): 922-930.
[3] Chen B W, Xiong J N, Zhi X, et al. WZ4003 sensitizes hepatocellular carcinoma to OSI-027 by inhibiting ARK5-mediated autophagy[J]. Cancer Letters, 2025: 217989.
[4] Zhi X, Chen W, Xue F, et al. OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo[J]. Oncotarget, 2015, 6(28): 26230.
[5] Lou J, Lv J X, Zhang Y P, et al. OSI‐027 inhibits the tumorigenesis of colon cancer through mediation of c‐Myc/FOXO3a/PUMA axis[J]. Cell Biology International, 2022, 46(8): 1204-1214.
[6] Chen B W, Chen W, Liang H, et al. Inhibition of mTORC2 induces cell-cycle arrest and enhances the cytotoxicity of doxorubicin by suppressing MDR1 expression in HCC cells[J]. Molecular cancer therapeutics, 2015, 14(8): 1805-1815.
[7] Liang M, Dang H, Li Q, et al. Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury[J]. Biochemical and Biophysical Research Communications, 2021, 556: 39-44.
[8] Zhang Y, Wang X, Qin X, et al. PP2AC level determines differential programming of p38-TSC-mTOR signaling and therapeutic response to p38-targeted therapy in colorectal cancer[J]. EBioMedicine, 2015, 2(12): 1944-1956.
OSI-027是一种选择性小分子口服抑制剂，可同时抑制mTORC1和mTORC2的激酶活性，IC50值分别为22nM和65nM[1]。OSI-027能阻断mTORC1/2的激活，导致磷酸化Akt、磷酸化p70S6k、磷酸化4EBP1、细胞周期蛋白D1以及cyclin-dependent kinase4 (CDK4)的表达下调[2]。OSI-027 已作为一种抗癌剂，广泛用于抑制异种移植动物模型中的肿瘤生长[3]。
在体外，OSI-027处理24小时显著降低了Panc-1、BxPC-3和CFPAC-1细胞的细胞活力，IC50值分别为21.57μM、8.360μM和13.72μM[4]。用10μM的OSI-027处理48小时诱导了HCT116和SW620细胞的凋亡，显著上调了细胞中Bax、Bim、cleaved-caspase 3、FOXO3a和PUMA的蛋白水平[5]。用4μM的OSI-027处理48小时诱导了Hep-3B细胞的细胞周期阻滞，并抑制了Hep-3B细胞中mTORC1底物的磷酸化，包括4E-BP1（Thr37/46）和p70S6K（Thr389）[6]。
在体内，OSI-027以0.5mg/kg剂量（每周三次）腹腔注射连续两周，显著减少了高氧诱导的幼年大鼠肺损伤模型中肺泡腔和肺泡间隔的炎症，减轻了肺损伤和纤维化[7]。每日腹腔注射10mg/kg剂量的OSI-027和5mg/kg剂量的SB202190连续12天，可显著抑制异种移植SW620肿瘤小鼠的肿瘤生长并诱导肿瘤细胞凋亡[8]。
| Cell experiment [1]: | |
Cell lines | BxPC-3 cells |
Preparation Method | BxPC-3 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin, and were maintained in a humidified incubator at 37°C and 5% CO2. The cells were seeded at a density of 3000 cells per well in a 96-well plate and were separately treated with OSI-027 (0, 1.25, 2.5, 5, 10, 20, 40 and 80μM). The cytotoxicity of OSI-027 was then detected 24, 48 and 72 hours after the drug treatment. |
Reaction Conditions | 0, 1.25, 2.5, 5, 10, 20, 40 and 80μM; 24, 48, and 72h |
Applications | OSI-027 treatment inhibited the proliferation of BxPC-3 cells in a concentration and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley (SD) rat |
Preparation Method | Seventy-two SD rat pups (3 weeks old) were randomly assigned to the following groups: air+normal saline group (air group); hyperoxia + normal saline group (hyperoxia group); and hyperoxia+OSI-027 group (hyperoxia OSI group). The hyperoxia-exposed SD pups in each group were placed in a homemade plastic oxygen incubator (60cm×50cm×40cm), and 99.9% high-purity medical oxygen was continuously introduced into the air inlet of the incubator to maintain the oxygen volume fraction at 90%. The environmental temperature was 25℃-27℃, and the humidity was 60%-70%. At 9:30 every morning, the incubator was opened for 30 minutes, and the rats' dressings were changed, water and food were added. The rats in the air group and the hyperoxia group were intraperitoneally injected with 0.5ml normal saline. The rats in the hyperoxia OSI group were intraperitoneally injected with OSI-027 (0.5mg/kg; three times a week) for 2 weeks. One hour after the injection, the rats were exposed to hyperoxia (FiO2=0.90) or air (FiO2=0.21). |
Dosage form | 0.5mg/kg; three times a week for 2 weeks; p.o. |
Applications | OSI-027 treatment alleviated hyperoxia-induced lung injury and fibrosis in SD rat pups. |
References: | |
| Cas No. | 936890-98-1 | SDF | |
| 别名 | 反式-4-[4-氨基-5-(7-甲氧基-1H-吲哚-2-基)咪唑并[5,1-F][1,2,4]三嗪-7-基]环己烷羧酸,ASP7486 | ||
| 化学名 | 4-[(5Z)-4-amino-5-(7-methoxyindol-2-ylidene)-1H-imidazo[5,1-f][1,2,4]triazin-7-yl]cyclohexane-1-carboxylic acid | ||
| Canonical SMILES | COC1=CC=CC2=CC(=C3C4=C(N=CNN4C(=N3)C5CCC(CC5)C(=O)O)N)N=C21 | ||
| 分子式 | C21H22N6O3 | 分子量 | 406.45 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 80 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml,Ethanol: 0.1 mg/ml | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4603 mL | 12.3016 mL | 24.6033 mL |
| 5 mM | 492.1 μL | 2.4603 mL | 4.9207 mL |
| 10 mM | 246 μL | 1.2302 mL | 2.4603 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet