Identification of inhibitors targeting the FLT3-ITD mutation through 4D-QSAR, in vitro, and in silico.

The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation is a key target for acute myeloid leukemia (AML) treatment. The second-generation inhibitors such as Gilteritinib still present off-target effects and associated side effects. Therefore, identifying novel FLT3-ITD inhibitors has become a promising strategy for AML treatment.

Visible-Light-Driven [2 + 2] Photocycloaddition for Constructing Dimers of ,'-Diacyl-1,4-dihydropyrazines: Experimental and Theoretical Investigation.

In this study, the visible-light-driven [2 + 2] photocycloaddition of 1,4-dihydropyrazines in solution was reported. The ,-diacyl-1,4-dihydropyrazines with different substituents showed completely different reactivity under the irradiation of a 430 nm blue light-emitting diode (LED) lamp. ,'-Diacetyl-1,4-dihydropyrazine and ,'-dipropionyl-1,4-dihydropyrazine were the only compounds capable of undergoing a [2 + 2] photocycloaddition reaction, yielding syn-dimers and cage-dimers (known as 3,6,9,12-tetraazatetraasteranes) with overall yields of 76 and 83%, correspondingly.

Synthesis and anti-HIV-1 activity evaluation of Keggin-type polyoxometalates with amino acid as organic cations.

Polyoxometalates (POMs), as a class of multinuclear metal oxygen clusters, have promising biological activities. And their amino acid derivatives will lead to better pharmacological activity by the diversity in structures and properties. With reference to the anti-HIV-1 activities of PM-19 (KPTiWO) and its pyridinium derivatives, a series of novel Keggin-type POMs with amino acid as organic cations (APTiWO) were synthesized by hydrothermal synthetic method.

4D-QSAR and MIA-QSAR study on the Bruton's tyrosine kinase (Btk) inhibitors.

In this paper, 4D-QSAR analysis base on LQTA-QSAR method and MIA-QSAR analysis were presented. And a combination model of 4D-QSAR model and MIA-QSAR model with better predictive performance was built. The 4D-QSAR descriptors were obtained by calculating the interaction energies between the probes and aligned conformational ensemble profiles (CEP) resulting from molecular dynamics simulation.