Rene Raphemot

TL;DR: Takinib is a potent and selective TAK1 inhibitor that induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer and is an attractive starting point for the development of inhibitors that sensitize cells to T NF-α-induced cell death, with general implications for cancer and autoimmune disease treatment.

TL;DR: It is demonstrated that renal failure is a promising mechanism of action for killing mosquitoes, and the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides is motivated.

TL;DR: Proof-of-concept that potent and highly selective inhibitors of mosquito Kir channels can be developed using conventional drug discovery approaches is demonstrated and reinforces the notion that the physical and chemical properties that determine a compound's bioavailability in vivo will be critical in determining the efficacy of Kir channel inhibitors as insecticides.

TL;DR: A thallium (Tl+) flux-based high-throughput screen of a Kir1.1 inhibitor library for modulators of GIRK revealed few analogs with improved potency, however two compounds retained most of their activity toward GirK and Kir2.1, and the structure–activity relationships of VU573 will be useful for exploring the physiology and structure–function relationships of these Kir channels.

TL;DR: Pharmacological validation of a specific mosquito Kir channel (AeKir1) in the yellow fever mosquito Aedes aegypti is provided, showing that VU590, a small-molecule inhibitor of mammalian Kir1.1 and Kir7.1 channels, potently inhibits AeK Kir1 but not another mosquito Kir channels (AoKir2B) in vitro.