NV03
目录号 : GC64772NV03 是一种有效,选择性的 UHRF1 与 H3K9me3 相互作用的拮抗剂,Kd 值为 2.4 μM。NV03 有抗癌活性。
Cas No.:2448341-58-8
Sample solution is provided at 25 µL, 10mM.
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NV03 is a potent and selective antagonist of UHRF1 (Ubiquitin-like with PHD and RING finger domains 1)- H3K9me3 interaction by binding to UHRF1 tandem tudor domain, with a Kd of 2.4 μM. NV03 has anticancer activity[1].
[1]. Senisterra G, et al. Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain. SLAS Discov. 2018 Oct;23(9):930-940.
Cas No. | 2448341-58-8 | SDF | Download SDF |
分子式 | C19H27N5O2S | 分子量 | 389.51 |
溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.5673 mL | 12.8366 mL | 25.6733 mL |
5 mM | 0.5135 mL | 2.5673 mL | 5.1347 mL |
10 mM | 0.2567 mL | 1.2837 mL | 2.5673 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) | ||||||||||
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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。
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Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain
SLAS Discov 2018 Oct;23(9):930-940.PMID:29562800DOI:10.1177/2472555218766278
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a multidomain protein that plays a critical role in maintaining DNA methylation patterns through concurrent recognition of hemimethylated DNA and histone marks by various domains, and recruitment of DNA methyltransferase 1 (DNMT1). UHRF1 is overexpressed in various cancers, including breast cancer. The tandem tudor domain (TTD) of UHRF1 specifically and tightly binds to histone H3 di- or trimethylated at lysine 9 (H3K9me2 or H3K9me3, respectively), and this binding is essential for UHRF1 function. We developed an H3K9me3 peptide displacement assay, which was used to screen a library of 44,000 compounds for small molecules that disrupt the UHRF1-H3K9me3 interaction. This screen resulted in the identification of NV01, which bound to UHRF1-TTD with a Kd value of 5 μM. The structure of UHRF1-TTD in complex with NV01 confirmed binding to the H3K9me3-binding pocket. Limited structure-based optimization of NV01 led to the discovery of NV03 (Kd of 2.4 μM). These well-characterized small-molecule antagonists of the UHRF1-H3K9me2/3 interaction could be valuable starting chemical matter for developing more potent and cell-active probes toward further characterizing UHRF1 function, with possible applications as anticancer therapeutics.