BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: BCR-ABL tyrosine kinase (BCR-ABL); dengue virus envelope protein E (DENV_gp1)

May 26, 2016 7:00 AM UTC

Cell culture studies identified dual inhibitors of BCR-ABL and DENV_gp1 that could help treat dengue infection. Previous studies in dengue virus-infected hamster kidney fibroblasts identified an allosteric inhibitor of BCR-ABL that decreased viral growth compared with the BCR-ABL inhibitor Gleevac imatinib. Chemical synthesis and testing in mammalian cell-based viral infectivity assays of disubstituted pyrimidine analogs of the allosteric inhibitor identified three compounds that inhibited growth of dengue virus serotypes 1 and 2 with IC90 values of 1-5 µM. In in vitro binding assays, additional analogs of the allosteric inhibitor bound to DENV_gp1 with higher affinity than the parent compound. Next steps include optimizing and testing the compounds in animal models of dengue viral infection...