Abstract: The present invention provides pyridine and pyrazine derivatives which restore or enhance the function of mutant and/or wild type CFTR to treat bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, chronic bronchitis, chronic obstructive pulmonary disease, asthma, respiratory tract infections, lung carcinoma, xerostomia and keratoconjunctivitis sire, or constipation (IBS, IBD, opioid induced). Pharmaceutical compositions comprising such derivatives are also encompassed.

Abstract: Provided herein are compounds and pharmaceutical compositions useful for treating bronchiectasis, chronic obstructive pulmonary disorder, cystic fibrosis, chronic bronchitis or asthma comprising administering to a subject in need thereof a therapeutically effective amount of a compound or pharmaceutical composition described herein.

Abstract: Provided herein are compounds and pharmaceutical compositions useful for treating bronchiectasis, chronic obstructive pulmonary disorder, cystic fibrosis, chronic bronchitis or asthma comprising administering to a subject in need thereof a therapeutically effective amount of a compound or pharmaceutical composition described herein.

Abstract: The present invention provides pyridine and pyrazine derivatives which restore or enhance the function of mutant and/or wild type CFTR to treat bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, chronic bronchitis, chronic obstructive pulmonary disease, asthma, respiratory tract infections, lung carcinoma, xerostomia and keratoconjunctivitis sire, or constipation (IBS, IBD, opioid induced). Pharmaceutical compositions comprising such derivatives are also encompassed.

Abstract: A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein. In some embodiments the method can comprise inhibiting expression of the transport protein. Expression of the transport protein can be inhibited through introduction of a RNA having a sequence corresponding to a coding strand of the gene encoding the transport protein into the hepatocyte.

Abstract: A method of pulsing cultured hepatocytes, such as sandwich-cultured hepatocytes. The method includes providing a culture of hepatocytes, the culture having at least one bile canaliculus; exposing the culture of hepatocytes to a calcium-free buffer, whereby the contents of the at least one bile canaliculus are released; and removing the calcium-free buffer Pulsing cultured hepatocytes can reduce cholestasis arid can provide an in vitro culture of hepatocytes the more closely reflects in vivo hepatocyte characteristics.

Abstract: A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein. The method includes the steps of providing a culture of hepatocytes comprising a transport protein, the culture having at least one bile canaliculus; exposing a candidate compound to the culture; and determining an amount of candidate compound in the at least one bile canaliculus, the amount of candidate compound in the at least one bile canaliculus indicating the susceptibility of the candidate compound to biliary excretion by the transport protein. In some embodiments determining the amount of candidate compound in the bile canaliculus comprises inhibiting expression of the transport protein, measuring the amount of candidate compound in the bile canaliculus and comparing amounts of compound in the canalicules with and without inhibition of the transport protein.

Abstract: A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein. The method includes the steps of providing a culture of hepatocytes comprising a transport protein, the culture having at least one bile canaliculus; exposing a candidate compound to the culture; and determining an amount of candidate compound in the at least one bile canaliculus, the amount of candidate compound in the at least one bile canaliculus indicating the susceptibility of the candidate compound to biliary excretion by the transport protein. In some embodiments determining the amount of candidate compound in the bile canaliculus comprises inhibiting expression of the transport protein, measuring the amount of candidate compound in the bile canaliculus and comparing amounts of compound in the canalicules with and without inhibition of the transport protein.

Abstract: Methods and compositions for reducing or inhibiting, or preventing or delaying the onset of, one or more symptoms associated with an early and/or a late phase of an IL-13-associated disorder or condition using IL-13 binding agents are disclosed. Methods for evaluating the kinetics and/or efficacy of an IL-13 binding agent in treating or preventing an IL-13-associated disorder or condition in a subject, e.g., a human subject, are also disclosed.

Abstract: A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein. The method includes the steps of providing a culture of hepatocytes comprising a transport protein, the culture having at least one bile canaliculus; exposing a candidate compound to the culture; and determining an amount of candidate compound in the at least one bile canaliculus, the amount of candidate compound in the at least one bile canaliculus indicating the susceptibility of the candidate compound to biliary excretion by the transport protein. In some embodiments determining the amount of candidate compound in the bile canaliculus comprises inhibiting expression of the transport protein, measuring the amount of candidate compound in the bile canaliculus and comparing amounts of compound in the canalicules with and without inhibition of the transport protein.