Linperlisib (YY-20394)

Linperlisib (YY20394; PI3Kδ-IN-2)is a novel, potent, orally bioavailable, and highly selective PI3Kδ inhibitor that was being investigated in a phase I trial for patients with relapse or refractory B-cell malignancies. In vitro and in vivo growth inhibition of PI3K-expressing human tumor cells was achieved with the development of YY-20394. In immune-competent mice with 4T1 and CT26 tumors, YY-20394 also significantly reduced lung metastasis of 4T1 tumors with dose-dependent inhibition. T cells acted as a major mediator for YY-20394's anti-tumor effectiveness. More significantly, YY-20394 achieved long-term immune memory that is specific for CT26 tumors but not for unrelated A20 tumors, and it synergistically improved the anti-tumor efficacy of anti-PD-L1 antibody in the CT26 model. In vitro mechanistic studies revealed that YY-20394 significantly reduced T cell differentiation into Treg in both mouse splenocytes and primary CD4+ T cells from humans. It was also particularly effective at reducing their in vitro IL-10 secretion. Analysis of tumors treated with YY-20394 revealed that the drug reduced IL-10 secretion as well as the proportion of Treg in the leukocytes infiltrating the tumor. Additionally, it had some effects on the tumors' myeloid populations. These findings imply that the novel PI3Kδ inhibitor YY-20394 is a promising and secure immune modulator with significant promise as a cancer immunotherapeutic.

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.