Application of Integrated Drug Screening/Kinome Analysis to Identify Inhibitors of Gemcitabine-Resistant Pancreatic Cancer Cell Growth.

ABSTRACT: Continuous exposure of a pancreatic cancer cell line MIA PaCa-2 (Mia^S) to gemcitabine resulted in the formation of a gemcitabine-resistant subline (Mia^R). In an effort to discover kinase inhibitors that inhibited Mia^R growth, Mia^R cells were exposed to kinase inhibitors (PKIS-1 library) in a 384-well screening format. Three compounds (UNC10112721A, UNC10112652A, and UNC10112793A) were identified that inhibited the growth of Mia^R cells by more than 50% (at 50 nM). Two compounds (UNC10112721A and UNC10112652A) were classified as cyclin-dependent kinase (CDK) inhibitors, whereas UNC10112793A was reported to be a PLK inhibitor. Dose-response experiments supported the efficacy of these compounds to inhibit growth and increase apoptosis in 2

SUBMITTER: Krulikas LJ 

PROVIDER: S-EPMC6102050 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature