Description
IPI-145 is an inhibitor of p110δ PI3K that exhibits anticancer chemotherapeutic, immunosuppressive, and anti-inflammatory activities. In clinical trials, IPI-145 displays potential benefit in the treatment of chronic lymphocytic leukemia (CLL). IPI-145 inhibits proliferation of B and T cells, inhibits neutrophil migration, and prevents basophil activation in vitro. It also induces apoptosis in CLL cells. In animal models of inflammatory diseases, IPI-145 decreases levels of matrix metalloproteinase 13 (MMP13) and IL-17, inhibiting Th17 T cell differentiation and decreasing arthritis severity and progression.
References
Balakrishnan K, Peluso M, Fu M, et al. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL. Leukemia. 2015 Apr 28. [Epub ahead of print]. PMID: 25917267.
IPI-145 Shows Promise in CLL Patients. Cancer Discov. 2014 Feb;4(2):136. PMID: 24501284.
Boyle DL, Kim HR, Topolewski K, et al. Novel phosphoinositide 3-kinase δ,γ inhibitor: potent anti-inflammatory effects and joint protection in models of rheumatoid arthritis. J Pharmacol Exp Ther. 2014 Feb;348(2):271-80. PMID: 24244039.
Winkler DG, Faia KL, DiNitto JP, et al. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74. PMID: 24211136.
