Lee, Je-Heon published the artcileDiscovery of substituted indole derivatives as allosteric inhibitors of m6A-RNA methyltransferase, METTL3 -14 complex, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Drug Development Research (2022), 83(3), 783-799, database is CAplus and MEDLINE.
In this study, the discovery of the first allosteric inhibitor of the METTL3-14 complex I = [R1 = H, CH3; R2 = (4-methoxycarbonylphenoxy), (4-carbamoylphenoxy), (4-carboxyphenoxy), etc.] and II [R3 = 4-Cl-Ph, 4-F-phenyl; R4 = Ph, benzyl, [4-(3,5-dichlorophenyl)phenyl], etc] was described based on structure-activity relationship (SAR) and optimization studies of the hit compound, 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic acid. Compound II [R3 = 4-F-phenyl; R4 = [4-(3,5-dichlorophenyl)phenyl]] was optimized throughout the modifications of 4 different regions of the structure, and it displayed potent enzyme inhibitory activity of the METTL3-14 complex (IC50 = 2.81μM) and an antiproliferative effect in the AML cell lines by suppressing the m6A level of mRNA. The inhibition mechanism and binding mode of II [R3 = 4-F-phenyl; R4 = [4-(3,5-dichlorophenyl)phenyl]], were based on the interaction of the reversible and noncompetitive inhibitory profile at the allosteric site along with selectivity for the METTL3-14 complex relative to each subunit enzyme or truncated complex enzyme.
Drug Development Research published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Recommanded Product: 1H-Pyrazole-4-boronic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics