The present invention relates to selective inhibitors of PI3K delta protein kinases, methods of preparing them, pharmaceutical compositions containing them and methods of treatment and/or prevention of kinase mediated diseases or disorders with them.

The present invention relates to selective inhibitors of PI3K delta protein kinases, methods of preparing them, pharmaceutical compositions containing them and methods of treatment and/or prevention of kinase mediated diseases or disorders with them.

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.

The present invention relates to a purine compound useful as a kinase inhibitor. The compound has the structure:

##STR00001## or a pharmaceutically acceptable salt thereof

Methods of inhibiting phosphotidylinositol 3-kinase delta isoform (PI3K) activity, and methods of treating disease, such as disorders of immunity and inflammation, in which PI3K plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3K, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3K activity, including compounds that selectively inhibit PI3K activity. Methods of using PI3K inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3K inhibitory compounds to inhibit PI3K-mediated processes in vitro and in vivo.

The present invention relates to selective inhibitors of PI3K delta protein kinases, methods of preparing them, pharmaceutical compositions containing them and methods of treatment and/or prevention of kinase mediated diseases or disorders with them.

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.

Methods for reducing, inhibiting or preventing cancer metastasis comprise blocking the movement of mitochondria within a cancer cell. Other methods involve interrupting or preventing oxidative phosphorylation pathways or respiration pathways in the cancer cell. In one embodiment, mitochondrial movement is induced by contact of the cell with PI3K inhibitors or antagonists. Methods for treating cancer involve a regimen of treating a subject with a PI3K inhibitor or antagonist and treating the subject with a composition that blocks the movement of mitochondria within the subject's cells.

Provided is use of p55 gene and/or p55 protein as a target in maintaining cardiac iron homeostasis and treating a related disease, which belongs to the technical field of biomedicine. In the present disclosure, a p55 transgenic mice model and an ischemia/reperfusion (I/R) injury model in vivo and in vitro are used, and it is proposed that overexpression of p55 alleviates I/R injury induced cardiac ferroptosis, thereby protecting cardiac function. Moreover, it is found that the overexpression of p55 leads to downregulation of transferrin receptor 1 (Tfr1) by downregulating iron-regulatory protein 2 (IRP2), thereby maintaining the cardiac iron homeostasis to resist myocardial I/R injuries. This demonstrates a potential of the p55 gene and/or the p55 protein as a key regulator of I/R injury induced cardiomyocyte death, thereby providing new targets for maintaining the cardiac iron homeostasis and developing novel therapeutic approaches for related diseases.

The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3K inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3K) inhibitors and are therefore useful for the treatment and/or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors. ##STR00001##