Targeting the Allosteric Site of Oncoprotein BCR-ABL as an Alternative Strategy for Effective Target Protein Degradation was written by Shimokawa, Kenichiro;Shibata, Norihito;Sameshima, Tomoya;Miyamoto, Naoki;Ujikawa, Osamu;Nara, Hiroshi;Ohoka, Nobumichi;Hattori, Takayuki;Cho, Nobuo;Naito, Mikihiko. And the article was included in ACS Medicinal Chemistry Letters in 2017.COA of Formula: C14H23BN2O3 This article mentions the following:
Protein degradation technol. based on hybrid small mols. is an emerging drug modality that has significant potential in drug discovery and as a unique method of post-translational protein knockdown in the field of chem. biol. Here, we report the first example of a novel and potent protein degradation inducer that binds to an allosteric site of the oncogenic BCR-ABL protein. BCR-ABL allosteric ligands were incorporated into the SNIPER (Specific and Nongenetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers) platform, and a series of in vitro biol. assays of binding affinity, target protein modulation, signal transduction, and growth inhibition were carried out. One of the designed compounds, I (SNIPER(ABL)-062), showed desirable binding affinities against ABL1, cIAP1/2, and XIAP and consequently caused potent BCR-ABL degradation In the experiment, the researchers used many compounds, for example, 1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5COA of Formula: C14H23BN2O3).
1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5) belongs to tetrahydropyran derivatives. Dihydropyrans and tetrahydropyrans are examples of cyclic ethers widespread in nature. There is large number of marine macrolide natural products that contain tetrahydropyran and tetrahydrofuran ring together. For instance, goniodomin A (actin targeting polyether), prorocentrolide (toxin halistatins), and percentotoxineCOA of Formula: C14H23BN2O3
Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics