Dual protein kinase and nucleoside kinase modulators for rationally designed polypharmacology

Masitinib is a protein kinase inhibitor that sensitises refractory pancreatic adenocarcinoma cells to treatment with the nucleoside analog gemcitabine. Here the authors show that Masitinib activates deoxycytidine kinase to enhance phosphorylation of nucleoside analogue pro-drugs, increasing their potency

TET2 regulates immune tolerance in chronically activated mast cells

International audienc

Effect of Syk inhibitor AB8779 on production of IFN-α TNF-α and IL-6 in pDCs.

<p>(A) Experimental outline. GEN2.2 cells (B), or primary pDC (C) were incubated with different concentrations of Syk inhibitor AB8779 for 1 hr before stimulation with CpG-A, CpG-B and PMA (N = 3) (B), or CpG-A and R848 (N = 2) (<b>C</b>). After 16 hr culture, IFN-α TNF-α and IL-6 production in GEN2.2 cells (B) or in primary pDCs (C) was determined in cell-free supernatants by ELISA and the results expressed as a multiple of control with the matching concentration of DMSO.</p

Subliminal concentrations of Syk inhibitor partially restore IFN-α production in GEN2.2 pDC cell line.

<p>(A) Experimental outline. After separation from MS-5 feeder cells, GEN2.2 cells were incubated with 0.01 μM AB8779 or with a matching concentration of DMSO for 1 hr before exposure ILT7 or BDCA-2 mAb or HCV or HBV particles and stimulation with CpG-A. (B) After 16 hr culture, IFN-α production was determined in GEN2.2 cell-free supernatants by ELISA, and the results were standardized to the quantity of IFN-α produced by GEN2.2 exposed to isotype control Ab or mock-infected culture in the absence of AB8779 (N = 3). (C) IFN-α production determined in GEN2.2 exposed to ILT7 or BDCA-2 mAb or HCV or HBV particles (shown in B) was normalized to IFN-α production in the absence of AB8779 *, <i>p</i> ≤0.05; **, <i>p</i> <0.01.</p

Autosomal recessive primary microcephaly due to ASPM mutations: An update (vol 39, pg 319, 2018)

status: publishe