CAL-130 is a PI3Kδ and PI3Kγ inhibitor [IC50s: 1.3 and 6.1 nM].

p110β:56 nM, p110δ:1.3 nM, p110γ:6.1 nM, p110α:115 nM

CAL-130 selectively inhibits the catalytic domains of p110γ and p110δ (IC50s: 1.3 and 6.1 nM for p110δ and p110γ, 115 and 56 nM for p110α and p110β) without affecting other intracellular signaling pathways such as p38 MAPK or insulin receptor tyrosine kinase, which are essential for overall cell function and survival.

The clinical impact of inhibiting both PI3Kγ and PI3Kδ activities is assessed through the administration of CAL-130 to Lck/Pten^fl/fl mice suffering from established T cell acute lymphoblastic leukemia. Selection of mice for the survival study is based on criteria including poor health appearance, a white blood cell count exceeding 45,000/μL, presence of blast cells in peripheral blood smear, and over 75% of circulating cells being double-positive for Thy1.2 and Ki-67 markers. These mice are then treated with an oral dosage (10 mg/kg) of CAL-130 every eight hours for a week, and their health outcomes are monitored until they become moribund. Despite the short treatment period, CAL-130 significantly increases the median survival rate of these mice to 45 days, in stark contrast to the 7.5 days survival of the control group.