Umbralisib (TGR-1202) is a dual inhibitor of PI3K delta and CK1 epsilon
Umbralisib (TGR-1202) is an oral, once daily, dual inhibitor of PI3K delta and CK1 epsilon. The phosphoinositide-3-kinases (“PI3Ks”) are a family of enzymes involved in various cellular functions, including cell proliferation and survival, cell differentiation, intracellular trafficking, and immunity. There are four isoforms of PI3K (alpha, beta, delta, and gamma), of which the delta isoform is strongly expressed in cells of hematopoietic origin, and often implicated in B-cell related lymphomas.
Umbralisib has nanomolar potency to the delta isoform of PI3K and high selectivity over the alpha, beta, and gamma PI3K isoforms. Umbralisib also uniquely inhibits casein kinase 1 epsilon (CK1 epsilon), which may have both direct anti-cancer effects and may also modulate T-cell activity associated with immune-mediated adverse events seen with previous PI3K inhibitors. Currently approved PI3K delta inhibitors have been associated with autoimmune mediated toxicities such as liver toxicity, lung toxicity and colitis. We believe the specificity differences of umbralisib, as compared to the approved PI3K inhibitors, its unique inhibition of CK1 epsilon, as well as its distinct and patented chemical structure may differentiate umbralisib within the PI3K inhibitor class.
Umbralisib has demonstrated activity in preclinical models of hematologic malignancies as well as in clinical studies. Currently, umbralisib is being evaluated in Phase 2b and Phase 3 trials in patients with NHL and CLL.
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