M1001

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Chemical Structure| 874590-32-6 同义名 : -
CAS号 : 874590-32-6
货号 : A1176736
分子式 : C17H17N3O2S
纯度 : 99%+
分子量 : 327.4
MDL号 : MFCD06761257
存储条件：

Pure form Keep in dark place, sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(763.59 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Hypoxia-inducible factor-2 (HIF-2), a heterodimeric transcriptional protein consisting of HIF-2a 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. M1001 pushes the side chain of Tyr281 to the junction of the PASB domains. Of the two subunits, prompting Tyr281 (HIF-2a-PASB domain) and Tyr456 (ARNT-PASB domain) to form a hydrogen bond. The close distance between the sulfone moiety and Tyr307 makes M1002 more capable of forming hydrogen bond with Tyr307, which may be the reason why M1002 has better affinity and agonistic activity than M1001[1].786-O cells treated with M1001 showed modestly increased expression of HIF-2 target genes, producing the opposite response of PT2385. In 786-O cells, M1002 enhanced the expression of HIF-2 target genes with greater efficacy than M1001. M1001 and M1002 could reduce the physical association between HIF-2α and VHL. The reduced VHL binding to HIF-2α in the presence of agonists could be a result of the intrinsically weakened interactions between their proteins caused by the conformational changes induced in HIF-2α, or may be due to secondary effects the compounds may have in reducing proline hydroxylation levels on HIF-2α[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.05mL

0.61mL

0.31mL

15.27mL

3.05mL

1.53mL

30.54mL

6.11mL

3.05mL
参考文献

[1] Yancheng Yu, Quanwei Yu,et al. 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.

[2] Dalei Wu, Xiaoyu Su,et al. Bidirectional modulation of HIF-2 activity through chemical ligands. Nat Chem Biol. 2019 Apr;15(4):367-376.