The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-activated epithelial Cl- channel. GlyH-101 is a glycine hydrazide compound that inhibits CFTR with a Ki value of 4.3±0.9μM. The inhibitory potency of GlyH-101 against CFTR was reduced at more negative voltages, with Ki values of 1.4, 3.8, 5.0, and 5.6μM for voltages of +60, +20, −20, and −60mV, respectively.[3] GlyH-101 inhibited cAMP/PKA-activated Cl- current in a dose- and voltage-dependent manner with IC50 values of 0.3±1.5 and 5.1±1.3μM at +100 and −100mV, respectively.[4] GlyH-101 at a dosage of 10μM rapidly and reversibly inhibited forskolin-induced hyperpolarization in nasal potential differences in mice (CD1 strain).[3]
作用机制
The inhibition of CFTR by GlyH-101 involves direct CFTR pore occlusion at a site at or near the extracellular-facing pore surface.[3]
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