Umbralisib (TGR-1202) is an oral inhibitor of PI3K-delta and CK1-epsilon administered once daily. Umbralisib is presently being evaluated in patients with NHL and CLL in combination with other agents including ublituximab. The phosphoinositide-3-kinases (PI3Ks) are a family of enzymes involved in many important cellular functions, including cell proliferation and survival, cell differentiation, intracellular trafficking, and immunity.
There are 4 isoforms of PI3K (alpha, beta, delta, and gamma), of which the delta isoform is highly expressed in hematopoietic cells and malignant lymphoid diseases. Dysregulation of the PI3K pathway is among one of the most commonly mutated pathways across all of cancer biology. Umbralisib is highly selective for the delta isoform of PI3K and has limited to no impact on the other PI3K isoforms.
Umbralisib also inhibits casein kinase 1 epsilon (CK1-epsilon). CK1-epsilon is a major regulator of oncoprotein translation, which drives growth and survival of lymphoma cells, including c-Myc. Presently, umbralisib is being evaluated in phase 2b and phase 3 trials in patients with NHL and CLL, in combination with other agents including ublituximab.