M1002
目录号 : GC65046
M1002 是一种缺氧诱导因子-2 (HIF-2) 激动剂，可以增强 HIF-2 靶基因的表达。M1002 与脯氨酰羟化酶结构域 (PHD) 抑制剂可发挥协同作用。
Cas No.:823830-85-9
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
M1002 is a hypoxia-inducible factor-2 (HIF-2) agonist, and can enhance the expression of HIF-2 target genes. M1002 shows synergy with prolyl-hydroxylase domain (PHD) inhibitors[1].
M1002 (10 μM; 24 h) enhances the expression of HIF-2 target genes with great efficacy[1].M1002 (5 μM; 24 h) treatment shows synergy with prolyl hydroxylase domain (PHD) inhibitors[1].
[1]. Dalei Wu, et al. Bidirectional modulation of HIF-2 activity through chemical ligands. Nat Chem Biol. 2019 Apr;15(4):367-376.
| Cas No. | 823830-85-9 | SDF | Download SDF |
| 分子式 | C15H8F6N2O2S | 分子量 | 394.29 |
| 溶解度 | 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 | 2.5362 mL | 12.681 mL | 25.362 mL |
| 5 mM | 0.5072 mL | 2.5362 mL | 5.0724 mL |
| 10 mM | 0.2536 mL | 1.2681 mL | 2.5362 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。
Insight into the binding mode of HIF-2 agonists through molecular dynamic simulations and biological validation
Eur J Med Chem 2021 Feb 5;211:112999.PMID:33189439DOI:10.1016/j.ejmech.2020.112999.
Hypoxia-inducible factor-2 (HIF-2), a heterodimeric transcriptional protein consisting of HIF-2α and aryl hydrocarbon receptor nuclear translocator (ARNT) subunits, has a broad transcriptional profile that plays a vital role in human oxygen metabolism. M1001, a HIF-2 agonist identified by high-throughput screening (HTS), is capable of altering the conformation of Tyr281 of the HIF-2α PAS-B domain and enhancing the affinity of HIF-2α and ARNT for transcriptional activation. M1002, an analog of M1001, shows improved efficacy than M1001. However, the cocrystal structure of M1001 and HIF-2 has some defects in revealing the agonist binding mode due to the relatively low resolution, while the binding mode of M1002 remained unexplored. To in-depth understand agonist binding profiles, herein, the molecular dynamic (MD) simulations was applied to construct a stable agonist-protein model, and a possible binding mode was proposed through the analysis of the binding free energy and hydrogen bonding of the simulation results. Nine compounds were then synthesized and evaluated to verify the proposed binding mode. Among them, compound 10 manifested improved agonistic activity and reduced toxicity compared to M1002. This study provides deep insight into the binding mode of such HIF-2 agonists, which would be useful for designing novel agonists for HIF-2.
Poly[(μ(5)-3,5-dinitro-benzoato)rubidium]
Acta Crystallogr Sect E Struct Rep Online 2011 Jul 1;67(Pt 7):M1002.PMID:21836829DOI:10.1107/S1600536811023026.
The asymmetric unit of the title compound, [Rb(C(7)H(3)N(2)O(6))](n), comprises an Rb cation and a 3,5-dinitro-benzoate anion. The Rb cation is eight-coordinated by O atoms from five 3,5-dinitro-benzoate anions. On the other hand, each 3,5-dinitro-benzoate anion links five Rb cations with the carboxyl-ate groups as μ(3)-bridging. The metal atom is firstly linked by the carboxyl-ate groups into a chain along the c-axis direction, which is further linked by bonds between the Rb and nitro O atoms, giving a three-dimensional framework.