Kharbanda, Anupreet published the artcileDiscovery of 4-aminoquinolines as highly selective TGFβR1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology, Formula: C3H5BN2O2, the publication is European Journal of Medicinal Chemistry (2021), 113763, database is CAplus and MEDLINE.
The tumor microenvironment contains high concentrations of TGFβ, a crucial immunosuppressive cytokine. TGFβ stimulates immune escape by promoting peripheral immune tolerance to avoid tumoricidal attack. Small-mol. inhibitors of TGFβR1 are a prospective method for next-generation immunotherapies. In the present study, we identified selective 4-aminoquinoline-based inhibitors of TGFβR1 through structural and rational-based design strategies. This led to the identification of [N-(2-(2,5-difluorophenyl)pyridin-4-yl)-7-(4-(methylsulfonyl)phenyl)quinolin-4-amine], which was found to be selective for TGFβR1 with the exception of MAP4K4 in the kinase profiling assay. The compound was then further optimized to remove MAP4K4 activity, since MAP4K4 is vital for proper T-cell function and its inhibition could exacerbate tumor immunosuppression. Optimization efforts led to [7-(4-(methylsulfonyl)phenyl)-N-(2-(m-tolyl)pyridin-4-yl)quinolin-4-amine] that inhibited TGFβR1 at an IC50 of 0.79 ± 0.19 nM with 2000-fold selectivity against MAP4K4. 7-(4-(Methylsulfonyl)phenyl)-N-(2-(m-tolyl)pyridin-4-yl)quinolin-4-amine, represents a highly selective TGFβR1 inhibitor that has potential applications in immuno-oncol.
European Journal of Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Formula: C3H5BN2O2.
Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics