BIX 02188 synthesis No specific inhibitor of KCC

No specific inhibitor of KCC has progressed to clinical trials, however, although compounds like H74 were shown to specifically target KCC over the related Na+-K+-2Cl− cotransporter (NKCC) (Ellory et al., 1990). This molecule, or its related analogues, represent compounds of promise. Simple Mg supplementation has also been used in limited clinical trials, as elevated red cell Mg inhibits KCC activity, with some success (De Franceschi et al., 1997, De Franceschi et al., 2000). If KCC activity BIX 02188 synthesis implicated as a key mechanism in pathogenesis, of particular importance in HbSC patients, re-evaluation of potential KCC inhibitors is warranted. An alternative approach has involved the development of compounds that directly interpolate with HbS molecules, to increase oxygen affinity and to reduce polymerisation upon deoxygenation. Aromatic aldehydes have shown promise and one of them, 5-hydroxymethyl-2-furfural (5HMF), is currently in phase II clinical trials in SCD patients in the US and UK (Abdulmalik et al., 2005, Stern et al., 2012, Health NIH, 2013, Safo and Kato, 2014). We have recently shown that it has additional effects on K+ transport, with inhibition of Psickle and Gardos channel and increased hydration, in red cells from SCD patients (Hannemann et al., 2014).
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