In 2018,Sameshima, Tomoya; Yamamoto, Takeshi; Sano, Osamu; Sogabe, Satoshi; Igaki, Shigeru; Sakamoto, Kotaro; Ida, Koh; Gotou, Mika; Imaeda, Yasuhiro; Sakamoto, Junichi; Miyahisa, Ikuo published 《Discovery of an Irreversible and Cell-Active BCL6 Inhibitor Selectively Targeting Cys53 Located at the Protein-Protein Interaction Interface》.Biochemistry published the findings.Reference of tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate The information in the text is summarized as follows:
B-cell lymphoma 6 (BCL6) is the most frequently involved oncogene in diffuse large B-cell lymphomas (DLBCLs). BCL6 shows potent transcriptional repressor activity through interactions with its corepressors, such as BCL6 corepressor (BCOR). The inhibition of the protein-protein interaction (PPI) between BCL6 and its corepressors suppresses the growth of BCL6-dependent DLBCLs, thus making BCL6 an attractive drug target for lymphoma treatments. However, potent small-mol. PPI inhibitor identification remains challenging because of the lack of deep cavities at PPI interfaces. This paper reports the discovery of a potent, cell-active, small-mol. BCL6 inhibitor, BCL6-i (8), that operates through irreversible inhibition. First, we synthesized an irreversible lead compound 4, which targets Cys53 in a cavity on the BCL6 BTB domain dimer by introducing an irreversible warhead to a high-throughput screening hit compound 1. Further chem. optimization of 4 based on kinact/KI evaluation produced BCL6-i with a kinact/KI value of 1.9 × 104 M-1s-1, corresponding to a 670-fold improvement in potency compared to 4. By exploiting the property of irreversible inhibition, engagement of BCL6-i to intracellular BCL6 was confirmed. BCL6-i showed intracellular PPI inhibitory activity between BCL6 and its corepressors, thus resulting in BCL6-dependent DLBCL cell-growth inhibition. BCL6-i is a cell-active chem. probe with the most potent BCL6 inhibitory activity reported to date. The discovery process of BCL6-i illustrates the utility of irreversible inhibition for identifying potent chem. probes for intractable target proteins. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6Reference of tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate)
tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6) belongs to ethers.Ethers do have nonbonding electron pairs on their oxygen atoms, and they can form hydrogen bonds with other molecules (alcohols, amines, etc.) that have O―H or N―H bonds. Reference of tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate The ability to form hydrogen bonds with other compounds makes ethers particularly good solvents for a wide variety of organic compounds and a surprisingly large number of inorganic compounds.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem