amTCO, a new trans-cyclooctene derivative to study drug-target interactions in cells.

Click chemistry probes have improved the study of drug interactions in live cells and relevant disease models. Proper design of the probes, including the choice of the click moiety coupled to the drug, is crucial to ensure good performance and broad application. A new trans-cyclooctene derivative, amTCO, was synthesised via a novel route using a phthalimide protecting group as a built-in photosensitiser for the cyclooctene isomerization.

ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma.

Background: Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC.

Toluidinesulfonamide hypoxia-induced factor 1 inhibitors: alleviating drug-drug interactions through use of PubChem data and comparative molecular field analysis guided synthesis.

Inhibitors of hypoxia-inducible factor 1 (HIF-1) represent promising anticancer therapeutics. We have identified a series of potent toluidinesulfonamide HIF-1 inhibitors. However, the series was threatened by a potential liability to inhibit CYP2C9 which could cause dangerous drug-drug interactions when being coadministered with other drugs.