2,5-dimethylcelecoxib

K_V7 (KCNQ) channels are voltage-gated potassium channels. These channels are mainly responsible for the cardiac and auditory IKs current and the neuronal M-current but can be found in other tissues as well. Voltage-gated potassium channels are tetramers of α-subunits, which surround a K⁺-selective pore¹. The five different KCNQ subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain tail. This domain is a self-assembling, parallel, four-stranded coiled coil².

2,5-Dimethylcelecoxib (DMC) is a synthetic opener of KCNQ channels in smooth muscle cells. It is a derivative of Celecoxib without its COX-2 inhibitory function. In asthma and other lung diseases, airways become hyperconstricted because of the secretion of various endogenous substances. DMC causes an increase in KCNQ currents and restores current amplitudes in guinea pig ASMC (air smooth muscle cells). This effect is also seen after the application of bronchoconstrictors such as methacholine and histamine, suggesting that DMC can regulate and dilate airway diameter in bronchoconstricting diseases³. DMC is a potent activator of apoptotic pathways and also suppresses production of prostaglandins in vitro by inhibiting cytokine-triggered upregulation of microsomal PGE-synthase-1. These properties may be valuable in the research of cancer⁴.