| Description | CAL-130 is a PI3Kδ and PI3Kγ inhibitor (IC50s: 1.3 and 6.1 nM). |
| In vitro | CAL-130 preferentially inhibits the function of both p110γ and p110δ catalytic domains (IC50s: 1.3 and 6.1 nM for p110δ and p110γ, 115 and 56 nM for p110α and p110β). CAL-130 does not inhibit additional intracellular signaling pathways (i.e., p38 MAPK or insulin receptor tyrosine kinase) that are critical for general cell function and survival. |
| In vivo | The clinical significance of interfering with the combined activities of PI3Kγ and PI3Kδ is determined by administering CAL-130 to Lck/Ptenfl/fl mice with established T cell acute lymphoblastic leukemia. Candidate animals for survival studies are ill-appearing, have a white blood cell count above 45,000/μL, evidence of blasts on peripheral smear, and a majority of circulation cells (>75%) staining double-positive for Thy1.2 and Ki-67. Mice receive an oral dose (10 mg/kg) of CAL-130 every 8 hr for a period of 7 days and are then followed until moribund. Despite the limited duration of therapy, CAL-130 is highly effective in extending the median survival for treated animals to 45 days as compared to 7.5 days for the control group. |
| Target activity | p110α:115 nM, p110γ:6.1 nM, p110δ:1.3 nM, p110β:56 nM |
| molecular weight | 426.47 |
| Molecular formula | C23H22N8O |
| CAS | 1431697-74-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Subramaniam Prem S, et al. Targeting nonclassical oncogenes for therapy in T-ALL. Cancer cell (2012), 21(4), 459-72. |