In Vitro

In vitro Activity: TGR-1202 causes a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM. In human lymphoma and leukemia cell lines, TGR-1202 (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner. TGR-1202 and carfilzomib synergistically kill blood cancer cells through disrupting the 4E-BP1-eIF4F-c-Myc axis. TGR-1202 and carfilzomib in combination synergistically and selectively silence the c-Myc and E2F transcription programs. TGR-1202 (15-50 μM) potently represses the expression of c-Myc in the DLBCL cell line LY7, and is uniquely characterized with structural features suitable for targeting CK1ε in lymphoma cells.

Kinase Assay: Umbralisib (TGR-1202) is a novel PI3Kδ inhibitor, with IC50 and EC50 of 22.2 nM and 24.3 nM, respectively; Umbralisib (TGR-1202) is also active against CK1ε, with an EC50 value of 6.0 μM.

Cell Assay: Multiple Myeloma resistant (MM-1R) or sensitive (MM-1S) cells are incubated with desired concentrations of RP5264. Growth is assessed after 96 h by a MTT assay.