Fig. 7: Combinations of the S1PR2 agonist CYM-5520 and the IRE1 inhibitor B-I09 show improved killing activity against primary mouse and human CLL cells.

A CLL cells purified from the spleens of Eμ-TCL1 mice (n = 4) were treated with 20 μM B-I09, 10 μM CYM-5520, or the combination of both for 3 days and subjected to XTT assays. Percentages of growth were determined by comparing drug-treated groups with control groups and data are shown as means ± SEM. B CLL cells purified from the spleens of Eμ-TCL1 mice were treated with 10 μM B-I09, 10 μM CYM-5520, or the combination of both for 24 h and lysates were immunoblotted for the indicated proteins. C The human OSU-CLL cell line was treated with 20 μM B-I09, 20 μM CYM-5520, or the combination of both for 3 days and subjected to XTT assays. Percentages of growth were determined by comparing drug-treated groups with control groups and data are shown as means ± SD. D–F Primary human CLL cells purified from the peripheral blood of 3 patients were treated with 20 μM B-I09, 10 μM CYM-5520, or the combination of both for 60 hours and subjected to XTT assays. Percentages of growth were determined by comparing drug-treated groups with control groups and data are shown as means ± SD. G Primary human CLL cells purified from the peripheral blood were treated with 20 μM B-I09, 10 μM CYM-5520, or the combination of both for 24 hours and lysates were immunoblotted for the indicated proteins.