GNE-6776

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Chemical Structure| 2009273-71-4 同义名 : GEN-6776
CAS号 : 2009273-71-4
货号 : A955293
分子式 : C20H20N4O2
纯度 : 99%+
分子量 : 348.4
MDL号 : MFCD31657364
存储条件:

Pure form Keep in dark place, inert atmosphere, 2-8°C

In solvent -20°C:1个月-80°C:12个月

溶解度 : -
动物实验配方:
生物活性
描述 Deubiquitinase enzymes cleave ubiquitin from substrates and are implicated in disease; for example, ubiquitin-specific protease-7 (USP7) regulates stability of the p53 tumour suppressor and other proteins critical for tumour cell survival[2]. GNE-6776 is a selective USP7 inhibitor. It non-covalently targets USP7 12 Å distant from the catalytic cysteine and attenuates ubiquitin binding and thus inhibits USP7 deubiquitinase activity. GNE-6776 targets cellular USP7, MDM2, and p53 signaling pathways but selectively inhibits recombinant USP7 relative to 36 other deubiquitinases. Notably, GNE-6776 remains selective even at 100 μM, a more than sixfold higher concentration than used in cellular assays[2]. Although efficacious exposure is only transiently achieved, GNE-6776 causes modest, although significant, EOL-1 xenograft growth delay[2].
作用机制 GNE-6776 interacts with acidic residues that mediate hydrogen-bond interactions with the ubiquitin Lys48 side chain.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.87mL

0.57mL

0.29mL

14.35mL

2.87mL

1.44mL

28.70mL

5.74mL

2.87mL

参考文献

[1]Kategaya L, Di Lello P, Rougé L, et al. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017;550(7677):534-538.

[2]Kategaya L, Di Lello P, Rougé L, Pastor R, Clark KR, Drummond J, Kleinheinz T, Lin E, Upton JP, Prakash S, Heideker J, McCleland M, Ritorto MS, Alessi DR, Trost M, Bainbridge TW, Kwok MCM, Ma TP, Stiffler Z, Brasher B, Tang Y, Jaishankar P, Hearn BR, Renslo AR, Arkin MR, Cohen F, Yu K, Peale F, Gnad F, Chang MT, Klijn C, Blackwood E, Martin SE, Forrest WF, Ernst JA, Ndubaku C, Wang X, Beresini MH, Tsui V, Schwerdtfeger C, Blake RA, Murray J, Maurer T, Wertz IE. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017 Oct 26;550(7677):534-538. doi: 10.1038/nature24006. Epub 2017 Oct 18. PMID: 29045385.