Biological Activity
CFTR(inh)-172 is a potent and selective blocker of the CFTR chloride channel; reversibly inhibited CFTR short-circuit current in less than 2 minutes with a Ki of 300 nM.
In Vitro
Inhibition by CFTR(inh)-172 is complete in approximately 10 minutes (t1/2=4 minutes) and is reversed after ishout with t1/2 approximately 5 minutes. CFTRinh-172 is nontoxic to FRT cells after 24 hours at concentrations up to 100 μM[1]. CFTR(inh)-172 does not alter CFTR unitary conductance (8 pS), but reduces open probability by > 90% with Ki=0.6 μM. This effect is due to increased mean channel closed time without changing mean channel open time. The Ki values for inhibition of Cl- current in wild-type, G551D, and G1349D CFTR are about 0.5 μM; however, Ki is significantly reduced to 0.2 μM for vF508 CFTR[2].
In Vivo
A single intraperitoneal injection of CFTR(inh)-172 (250 μg/kg) in mice reduces by more than 90% cholera toxin–induced fluid secretion in the small intestine over 6 hours. CFTR(inh)-172 is nontoxic at high concentrations in mouse models. CFTRinh-172 significantly reduces fluid secretion to that in saline control loops, whereas an inactive CFTRinh-172 analog does not inhibit fluid secretion[1].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
