GDC-0941 dimethanesulfonate
(Synonyms: GDC-0941 (2 MeSO3H salt);GDC0941 dimethanesulfonate;GDC-0941;GDC0941;GDC 0941) 目录号 : GC16154
A pan inhibitor of class I PI3K isoforms
Cas No.:957054-33-0
Sample solution is provided at 25 µL, 10mM.
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GDC-0941 is a novel selective class I phosphatidylinositol-3-kinase (PI3K) inhibitor. Activation of PI3K/Akt signaling pathway is frequently associated with tumorigenesis. Deregulation of this pathway occurs frequently with a variety of cancers and may contribute to the resistance to many anticancer agents. [1] Developing novel small molecules that specifically block the PI3K/Akt pathway may inhibit tumor growth. GDC-0941 is designed to bind the ATP-binding pocket of PI3K and to prevent formation of phosphatidylinositol-3, 4, 5-triphosphate (PIP3), a second messenger that transmits PI3K downstream signals. [2, 3] It binds to PI3K in an ATP-competitive manner.
GDC-0941 is a potent small-molecule thieno [3, 2-d] pyrimidine inhibitor of the class I PI3K. It is highly selective against isoforms p110( and p110( with IC50 of 3 nM, and moderately selective against isoforms p110( and p110( with IC50s of 33 nM and 75 nM, respectively.
GDC-0941 inhibits cell proliferation in vitro and in vivo. It causes growth inhibition in a variety of cancer cell lines, including A2780, MDA-MB-361, PC3, and U87MG. [2] It also inhibits the growth of trastuzumab–sensitive and –resistant HER2-amplied cancer cells which harbor p110( mutations or PTEN loss. [4] GDC-0941 also reduces tumor volume in different xenograft models. [4]
GDC-0941 can be taken orally.
References:
[1]Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27:5497-5510.
[2]Folkes AJ, Ahmadi K, Alderton WK, et al. The identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 2008; 51: 5522-5532.
[3]Knight ZA, Shokat KM. Chemically targeting the PI3K family. Biochem Soc Trans. 2007; 35: 245-249.
[4]Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Br J Cancer. 2011; 104(7): 1116-25.
| Cell experiment: [1] | |
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Cell lines |
MDA-MB-231 and SKBR3 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 |
10 μM for MDA-MB-231 cells 1.25 μM for SKBR3 cells 72 hours |
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Applications |
The cytotoxicity was determined using MTT assay, after 72 h exposure to GDC-0941, ABT-737 and the combination. 10-times greater concentration of ABT-737 as a single agent resulted in a less than 50% increase in cytotoxicity. Regardless of the sensitivity to single agents, the combination of GDC-0941 and ABT-737 induced a more significant reduction of viable cells, indicating potent synergistic effect of GDC-0941 and ABT-737. |
| Animal experiment: [2] | |
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Animal models |
Female severe combined immunodeficient mice injected with breast cancer cells |
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Dosage form |
Oral administration, 100 or 150 mg/kg |
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Applications |
GDC-0941 showed excellent antitumor activity in xenograft models with HER2 amplification, PIK3CA mutations, or concomitant alterations in two pathway components (e.g., PTEN loss and PIK3CA mutation), but little or no effect in xenografts of basal-like KRAS mutant MDA-MB-231 cells. Treatment with GDC-0941 at a dose of 100 mg/kg substantially down-regulated levels of pAKT(S473) in xenograft tumors of both sensitive KPL-4 cells and resistant MDA-MB-231 cells after 1 hour, suggesting effective pharmacodynamic inhibition of PI3K signaling at this dose in both models. |
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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] Zheng L, Yang W, Zhang C, et al. GDC-0941 sensitizes breast cancer to ABT-737 in vitro and in vivo through promoting the degradation of Mcl-1. Cancer letters, 2011, 309(1): 27-36. [2] O'Brien C, Wallin J J, Sampath D, et al. Predictive biomarkers of sensitivity to the phosphatidylinositol 3′ kinase inhibitor GDC-0941 in breast cancer preclinical models. Clinical Cancer Research, 2010, 16(14): 3670-3683. | |
| Cas No. | 957054-33-0 | SDF | |
| 别名 | GDC-0941 (2 MeSO3H salt);GDC0941 dimethanesulfonate;GDC-0941;GDC0941;GDC 0941 | ||
| 化学名 | 4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine;methanesulfonic acid | ||
| Canonical SMILES | CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6.CS(=O)(=O)O.CS(=O)(=O)O | ||
| 分子式 | C25H35N7O9S4 | 分子量 | 705.85 |
| 溶解度 | ≥ 207.6 mg/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 | 1.4167 mL | 7.0837 mL | 14.1673 mL |
| 5 mM | 0.2833 mL | 1.4167 mL | 2.8335 mL |
| 10 mM | 0.1417 mL | 0.7084 mL | 1.4167 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet