GNE-955
目录号 : GC33253
GNE-955是有效的泛Pim激酶抑制剂，Ki分别为18，110，8nM。
Cas No.:1527523-39-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
GNE-955 is a potent pan Pim kinase inhibitor with Kis of 18, 110, 8 nM for Pim1, Pim2, Pim3, respectively.
Pim kinases have been identified as promising therapeutic targets for hematologic-oncology indications, including multiple myeloma and certain leukemia. MM.1S myeloma cell line treated with a dose range of GNE-955 reveals a constellation of PIM downstream signaling events consistent with inhibition of Pim kinases[1].
GNE-955 has excellent bioavailability in rat. Rat clearance of GNE-955 is moderate at 34 mL /min/kg with good oral exposure[1].
[1]. Wang X, et al. Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability. J Med Chem. 2017 May 25;60(10):4458-4473.
| Cas No. | 1527523-39-2 | SDF | |
| Canonical SMILES | CC1=CN=CC(C2=CC3=C(C=NN3C4=CC=C(OC)C(N5CCC[C@H](N)C5)=N4)C=N2)=N1 | ||
| 分子式 | C22H24N8O | 分子量 | 416.48 |
| 溶解度 | Soluble 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 | 2.4011 mL | 12.0054 mL | 24.0108 mL |
| 5 mM | 0.4802 mL | 2.4011 mL | 4.8022 mL |
| 10 mM | 0.2401 mL | 1.2005 mL | 2.4011 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。
Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability
J Med Chem 2017 May 25;60(10):4458-4473.PMID:28445037DOI:10.1021/acs.jmedchem.7b00418
Pim kinases have been identified as promising therapeutic targets for hematologic-oncology indications, including multiple myeloma and certain leukemia. Here, we describe our continued efforts in optimizing a lead series by improving bioavailability while maintaining high inhibitory potency against all three Pim kinase isoforms. The discovery of extensive intestinal metabolism and major metabolites helped refine our design strategy, and we observed that optimizing the pharmacokinetic properties first and potency second was a more successful approach than the reverse. In the resulting work, novel analogs such as 20 (GNE-955) were discovered bearing 5-azaindazole core with noncanonical hydrogen bonding to the hinge.