@entity1 upcyte   hepatocytes are proliferating hepatocytes that retain many characteristics of primary @entity1 hepatocytes. We conducted a comprehensive evaluation of the application of second-generation upcyte   hepatocytes from four donors for inhibition and induction assays using a selection of reference inhibitors and inducers. @entity4914 , @entity11670 , @entity5060 , and @entity5322 were reproducibly inhibited in a concentration-dependent manner and the calculated IC50 values for each compound correctly classified them as potent inhibitors. Upcyte   hepatocytes were responsive to prototypical @entity4914 , @entity11670 , @entity5060 , and @entity5322 inducers, confirming that they have functional AhR-, CAR-, and @entity16566 -mediated CYP regulation. A panel of 11 inducers classified as potent, moderate or noninducers of @entity5322 and @entity11670 were tested. There was a good fit of data from upcyte   hepatocytes to three different predictive models for @entity5322 induction, namely the Relative Induction Score (RIS), AUCu/F2, and C max,u/Ind50. In addition, @entity16566 ( @entity1215 ) and CAR-selective ( @entity2049 and @entity3174 ) inducers of @entity5322 and @entity11670 induction, respectively, were demonstrated. In conclusion, these data support the use of second-generation upcyte   hepatocytes for CYP inhibition and induction assays. Under the culture conditions used, these cells expressed CYP activities that were equivalent to or higher than those measured in primary @entity1 hepatocyte cultures, which could be inhibited or induced by prototypical CYP inhibitors and inducers, respectively. Moreover, they can be used to predict in  vivo @entity5322 induction potential using three prediction models. Bulk availability of cells from multiple donors makes upcyte   hepatocytes suitable for DDI screening, as well as more in-depth mechanistic investigations.

Applicability of second-generation upcyte   XXXX hepatocytes for use in CYP inhibition and induction studies.

@entity1 :: ('9606', 'Species') :: ['human', 'Human'] @entity11670 :: ('1555', 'Gene') :: ['CYP2B6'] @entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity16566 :: ('8856', 'Gene') :: ['PXR'] @entity2049 :: ('MESH:D002220', 'Chemical') :: ['carbamazepine'] @entity5060 :: ('1559', 'Gene') :: ['CYP2C9'] @entity3174 :: ('MESH:D010672', 'Chemical') :: ['phenytoin'] @entity1215 :: ('MESH:D012293', 'Chemical') :: ['rifampicin'] @entity4914 :: ('1544', 'Gene') :: ['CYP1A2']
@entity1 :: (9606,Species) :: ['human']
