选择性MAP3K1抑制剂促进NPM1作为网络成员的发现。

IF 4.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules Pub Date : 2025-04-30 DOI:10.3390/molecules30092001

Lidia Boghean, Sarbjit Singh, Kiran K Mangalaparthi, Smitha Kizhake, Lelisse Umeta, Donn Wishka, Paul Grothaus, Akhilesh Pandey, Amarnath Natarajan

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引用次数: 0

摘要

喹啉核心存在于几种生物活性化合物中，埃尔达非替尼是fda批准的第一个针对激酶并具有抗癌特性的喹啉衍生物。我们之前报道了一种喹啉类似物（84），通过抑制NFκB通路中的关键激酶IKKβ显示出抗癌作用。在这里，我们合成了一个区域异构体（51-106），并将其表征为具有改善代谢稳定性和口服生物利用度的选择性MAP3K1抑制剂。我们在蛋白质组学研究中使用小分子MAP3K1抑制剂，确定NPM1是MAP3K1网络的成员。

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A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network.

The quinoxaline core is found in several biologically active compounds, with Erdafitinib being the first FDA-approved quinoxaline derivative that targets a kinase and exhibits anti-cancer properties. We previously reported a quinoxaline analog (84) that displayed anti-cancer effects by inhibiting IKKβ, a key kinase in the NFκB pathway. Here, we present the synthesis of a regioisomer (51-106) and its characterization as a selective MAP3K1 inhibitor with improved metabolic stability and oral bioavailability. We used the small molecule MAP3K1 inhibitor in a proteomics study that identified NPM1 as a member of the MAP3K1 network.

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来源期刊

Molecules 化学-有机化学

CiteScore

7.40

自引率

8.70%

发文量

7524

审稿时长

1.4 months

期刊介绍： Molecules (ISSN 1420-3049, CODEN: MOLEFW) is an open access journal of synthetic organic chemistry and natural product chemistry. All articles are peer-reviewed and published continously upon acceptance. Molecules is published by MDPI, Basel, Switzerland. Our aim is to encourage chemists to publish as much as possible their experimental detail, particularly synthetic procedures and characterization information. There is no restriction on the length of the experimental section. In addition, availability of compound samples is published and considered as important information. Authors are encouraged to register or deposit their chemical samples through the non-profit international organization Molecular Diversity Preservation International (MDPI). Molecules has been launched in 1996 to preserve and exploit molecular diversity of both, chemical information and chemical substances.