BMS-754807
目录号 : GC16712
Dual inhibitor of IGF-1R and InsR tyrosine kinases
Cas No.:1001350-96-4
Sample solution is provided at 25 µL, 10mM.
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BMS-754807 is a potent and small molecular inhibitor which targets the IGF-1R/IR family kinases with Ki <2 nmol/L[1]. The efficacy of BMS-754807 on normal tissues and tumor cell cycle is believed to be different from the effects of continuous inhibition by anti-IGF-1R antibodies.[2]
BMS-754807 could effectively inhibit the growth of many human tumor types from in vitro perspective, such as mesenchymal, hematopoietic and epithelial tumor cell lines with an IC50 value of 5–365 nmol/L. It can also induce sub-G1 fraction accumulation and an increase in poly ADP ribose polymerase and Caspase 3 cleavage, suggesting that it can lead to apoptosis in a human rhabdomyosarcoma cell line (Rh41). Furthermore, as a pyrrolotriazine and reversible ATP-competitive antagonist of IGF-1R, BMS-754807 was shown to inhibit the catalytic domain of the IGF-1R, and proved to inhibit the IGF-1R and IR activity by using the in-vitro kinase assays. Since the antibodies can bind to IGF-1R but not to IR, this could be regardere as an escape mechanism for IGF-II and insulin signaling.[3]
References:
[1] Q.S. Chu，S.W. Kim，P.M. Ellis，L. Mileshkin，R.H. de Boer，J.S. Park，T. Pellas，F. Huang，F. Graf Finckenstein，A. Dhar. BMS-754807, an oral dual IGF-1R/insulin receptor (IR) inhibitor: initial results from a Phase 1 dose- and schedule-finding study in combination with carboplatin/paclitaxel in subjects with solid tumors. European Journal of Cancer Supplements. November 2010, 8(7): 131.
[2] Vattoly J. Majo, Victoria Arango, Norman R. Simpson, Jaya Prabhakaran, Suham A. Kassir, Mark D. Underwood, Mihran Bakalian, Peter Canoll, J. John Mann, J.S. Dileep Kumar. Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R. Bioorganic & Medicinal Chemistry Letters. July 2013, 23(14): 4191-4194.
[3] Joan M. Carboni, Mark Wittman, Zheng Yang, et al.. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009;8:3341-3349.
| Cell experiment: [1] | |
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Cell lines |
IGF-1R-Sal, Rh41 and Geo cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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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Reaction Conditions |
1 μM, (72 hours for cell proliferation inhibition; 1 hour for phosphorylation inhibition |
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Applications |
Cell proliferation was evaluated by incorporation of 3H-thymidine into DNA after exposure of cells to BMS-754807 with concentrations from 0.1 to 1000 nM. BMS-754807 inhibited cell proliferation with IC50 values of 7, 5 and 365 nM for IGF-1R-Sal, Rh41 and Geo cells, respectively. The IC50 values for inhibition of the pIGF-1R by BMS-754807 and downstream components (e.g., pAkt) were very similar. In contrast, there was greater inhibition against pMAPK in IGF-1R-Sal cells compared with Rh41 and Geo, indicating that additional compensatory pathways such as EGFR might be important in driving signals in both Rh41 and Geo cell types. |
| Animal experiment : [1] | |
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Animal models |
Nude mice bearing various tumor xenografts (Sal-IGF, GEO, Colo205, JJN3, Rh41 or RD1) |
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Dosage form |
Oral administration, 0.01 mL/g of body weight |
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Applications |
BMS-754807 inhibited tumor growth in a selected group of epithelial (IGF-1R-Sal, GEO and Colo205), hematopoietic (JJN3) and mesenchymal (RD1 and Rh41) xenograft tumor models with TGI ranging from 53% to 115%. In the highly sensitive Rh41 rhabdomyosarcoma, BMS-754807 was effective at a dose level of 3.125 mg/kg twice daily and as low as 6.25 mg/kg once daily. |
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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] Carboni J M, Wittman M, Yang Z, et al. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Molecular Cancer Therapeutics, 2009, 8(12): 3341-3349. |
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| Cas No. | 1001350-96-4 | SDF | |
| 化学名 | (2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide | ||
| Canonical SMILES | CC1(CCCN1C2=NN3C=CC=C3C(=N2)NC4=NNC(=C4)C5CC5)C(=O)NC6=CN=C(C=C6)F | ||
| 分子式 | C23H24FN9O | 分子量 | 461.49 |
| 溶解度 | ≥ 23.05mg/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 | 2.1669 mL | 10.8345 mL | 21.6689 mL |
| 5 mM | 0.4334 mL | 2.1669 mL | 4.3338 mL |
| 10 mM | 0.2167 mL | 1.0834 mL | 2.1669 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