|3-((2-(吡咯烷-1-基)苯基)氨基)苯并[d]异噻唑1,1-二氧化物|CsnPharm

CAS No.: 874590-32-6

M1001 Catalog No. CSN28806

Synonyms: M1001

M1001 is the first HIF-2 allosteric agonist, 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.

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

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].
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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 3.0544 mL
- 15.2718 mL
- 30.5436 mL
- 5 mM
- 0.6109 mL
- 3.0544 mL
- 6.1087 mL
- 10 mM
- 0.3054 mL
- 1.5272 mL
- 3.0544 mL

技术信息

CAS号	874590-32-6	储存条件	粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6 月 -80°C:12月
分子式	C17H17N3O2S	运输	蓝冰
分子量	327.40	别名	M1001

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

M1001 Catalog No. CSN28806

靶点选择性

请登录您的专属账户

确认信息