In vitro activity: LY3200882 is a next generation, ATP competitive, potent, highly selective small molecule inhibitor of TGF-β receptor type 1 (TGFβRI). It inhibits the serine-threonine kinase domain of TGFβRI. LY3200882 inhibits various pro-tumorigenic activities. LY3200882 potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells and in vivo in subcutaneous tumors in a dose dependent fashion. In preclinical tumor models, LY3200882 showed potent anti-tumor activity in the orthotopic 4T1-LP model of triple negative breast cancer and this activity correlated with enhanced tumor infiltrating lymphocytes in the tumor microenvironment.

Kinase Assay: In in vitro immune suppression assays, LY3200882 has shown the ability to rescue TGFβ1 suppressed or T regulatory cell suppressed naive T cell activity and restore proliferation. Therefore, LY3200882 shows promising activity as an immune modulatory agent. In addition, LY3200882 has shown anti-metastatic activity in vitro in migration assays as well as in vivo in an experimental metastasis tumor model (intravenous EMT6-LM2 model of triple negative breast cancer).

Cell Assay: LY3200882 is a next generation, ATP competitive, potent, highly selective small molecule inhibitor of TGF-β receptor type 1 (TGFβRI). It inhibits the serine-threonine kinase domain of TGFβRI. LY3200882 inhibits various pro-tumorigenic activities.