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
Dual mTORC1/mTORC2 inhibitor
Cas No.:936890-98-1
Sample solution is provided at 25 µL, 10mM.
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OSI-027 is a potent and selective inhibitor of mTORC1 and mTORC2 with IC50 values of 22nM and 65nM, respectively [1].
OSI-027 is developed as a potent anticancer agent through inhibiting mTORC1 and mTORC2. It shows more than 100-fold selectivity against mTOR over other PI3K-related kinases in biochemical assays. In cellular assays, OSI-027 inhibits the phosphorylation of mTORC1 and mTORC2 substrates including AKT, PRAS40 and S6K1, results in the blockade of downstream signaling. It shows equipotent cellular inhibition of both mTORC1 and mTORC2. It is demonstrated that OSI-027 is more potent in inhibiting cell proliferation and inducing cell death than rapamycin in a lot of tumor cell lines. Besides that, OSI-027 is also found to cause apoptosis via inducing sub-G1 fraction significantly. Furthermore, OSI-027 shows potent antitumor activity in MDA-MB-231 breast cancer xenograft model and human ovarian cancer xenograft models. The antitumor spectrum of OSI-027 is found to be quite broad including breast, colon, lung, prostate, lymphoma, and head and neck cancer [1].
References:
[1] Bhagwat S V, Gokhale P C, Crew A P, et al. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Molecular cancer therapeutics, 2011, 10(8): 1394-1406.
Kinase experiment: | Assays of a panel of 40 other recombinant kinases including both protein and lipid kinases are performed at 100 mM ATP concentration by SelectScreen profiling service. A broad panel of kinases is tested at a single concentration of OSI-027 or OXA-01 (3 μM) to evaluate percent inhibition of each kinase or mutant variant, using the Ambit KinomeScan platform[1]. |
Cell experiment: | To study the effect of drug treatment on cellular signaling, Ovcar-3 cells are plated in normal growth medium. After 24 hours, serum is removed and cells are serum-starved overnight. Rapamycin, OSI-027 and OXA-01 are solubilized in DMSO and added to cells at varying concentrations. After a two-hour incubation cells are growth factor stimulated with 10 ng/mL Insulin for 3 to 5 minutes, then rinsed with cold PBS and lysed[1]. |
Animal experiment: | Mice[1]For xenograft models, cells are harvested, implanted s.c. in the right flank of nu/nu CD-1 mice and tumor growth is analyzed. Mice bearing GEO xenografts are treated for 12 days with OSI-027 (65mg/kg) or vehicle and tumors collected at 2, 8, and 24 hours. Tumor growth inhibition and regression calculations are included. Rats[2]Specific pathogen-free female Lewis rats, male BN rats, male Lew-Tg(CAG-EGFP)YsRrrc rats and male Lew-TgYsRrrc rats are used. Orthotopic LT is undertaken. No antibiotics were used. Freshly prepared splenocytes (4×108, suspended in 500 μL PBS) of Lew-Tg YsRrrc rats are infused into each recipient via the dorsal penile vein immediately after LT (within 30 min). LTx-aGVHD model rats are divided into three experimental groups: RAPA (1 mg/kg), OSI-027 (1 mg/kg) or control (equal quantity of vehicle) groups; treatments are administered via the vena caudalis from day 7 to day 15. |
References: [1]. Falcon BL, et al. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83. | |
| 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: 10 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。 |
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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 | 2.4603 mL | 12.3016 mL | 24.6033 mL |
| 5 mM | 0.4921 mL | 2.4603 mL | 4.9207 mL |
| 10 mM | 0.246 mL | 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
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet