The University of North Carolina at Chapel Hill

Kim L R Brouwer

Edward L LeCluyse

Xingrong Liu

Peijin Zhang

Xianbin Tian

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.

Method for inhibiting expression of a protein in a hepatocyte

A method of screening a candidate compound for susceptibility to biliary excretion. The method includes the steps of providing a culture of hepatocytes, 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. Optionally, the culture of hepatocytes is a long-term culture in a sandwich configuration. The method is particularly applicable to the screening of multiple candidate compounds in a single effort.

Method of screening a metabolite of a parent candidate compound for susceptibility to biliary excretion

Method of screening candidate compounds for susceptibility to biliary excretion by endogenous transport systems

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. A difference in the amount of candidate compound in the canaliculus indicates susceptibility of the candidate compound to biliary excretion by the transport protein. In one embodiment, expression of the transport protein is inhibited through introduction of a RNA having a sequence corresponding to a coding strand of the gene encoding the transport protein into the hepatocyte. Optionally, the culture of hepatocytes is a long-term culture in a sandwich configuration. The method is particularly applicable to the screening of multiple candidate compounds in a single effort.

Growing community of inventors

Chapel Hill, NC, United States of America

Kim L R Brouwer