The present disclosure relates to the use of phosphoinositide 3-kinase (PI3K) inhibitors targeting allosteric and normal pockets of PI3K in methods of treating, preventing, or ameliorating diseases or conditions in which PI3K functions (or in use in treating, preventing, or ameliorating diseases or conditions). The PI3K inhibitors can be used in combination and can target allosteric or normal pockets of PI3K alpha simultaneously, separately, or sequentially. In some aspects of the disclosed methods, PI3K [alpha] inhibitors may target an allosteric or normal pocket of a PI3K [alpha] mutant that is resistant to treatment with another PI3K [alpha] inhibitor that targets a different pocket of PI3K [alpha].
The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosinekinase (BTK), interleukin-2-inducible T cellkinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.
This application relates to antibodies or antigen-binding fragments thereof that bind to phosphoinositide-3 -kinase interacting protein 1 (PIK3IP1) protein or antigen-binding fragments, as well as polynucleotides and vectors that encode for such antibodies or antigen-binding fragments. This application further relates to methods of producing the antibodies or antigen- binding fragments and using the antibodies or antigen-binding fragments for treatment of diseases.
The present invention relates to an alkyne derivative, a preparation method for same, and applications thereof in medicine. Specifically, the present invention relates to the alkyne derivative as represented by formula (I), the preparation method for same, a pharmaceutically acceptable salt thereof, and uses of them as a therapeutic agent, specifically as a phosphoinositide 3-kinase γ (PI3Kγ) inhibitor, where the definitions of the substituents in formula (I) are identical to the definitions in the description.
The invention discloses a phosphoinositide 3-kinase allosteric inhibitor for treating diseases related to PI3K (phosphoinositide 3-kinase) regulation, and particularly provides a compound shown as a formula I or a pharmaceutically acceptable salt thereof. The phosphoinositide 3-kinase allosteric inhibitor can effectively inhibit PI3K alphamutation, especially PI3K alpha H1047R mutation in an allosteric targeting mode, has good selectivity and is expected to treat and / or prevent related diseases or obstacles.
Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure:or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.
The invention refers to the field of neurodegenerative diseases including Alzheimer's Disease and a treatment thereof with a Benzoxazepine compound. Benzoxazepine compounds are e.g. known in the treatment of breast cancer and according to the use of the invention are a first therapeutic and prophylactic treatment for neurodegenerative diseases, including Alzheimer's Disease. The invention further relates to test systems for identifying, mapping, elaborating and evaluating said and further therapeutic and prophylactic uses of compounds of interest and / or other pharmaceutical compositions for the treatment of neurodegenerative diseases, including Alzheimer's Disease. (AD)
The present disclosure relates to compounds of Formula (I) or a prodrug, solvate, enantiomer, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, useful for treating diseases or disorders associated with PI3K modulation as allosteric chromenone inhibitors of phosphoinositide 3-kinases (PI3K), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, W, X, Y, s, and ring A are as described herein.
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosinekinase (BTK) inhibitor, and / or a B-celllymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
The present disclosure relates to the use of phosphoinositide 3-kinase (PI3K) inhibitors targeting allosteric and normal pockets of PI3K in methods of treating, preventing, or ameliorating diseases or conditions in which PI3K functions (or in use in treating, preventing, or ameliorating diseases or conditions). The PI3K inhibitors can be used in combination and can target allosteric or normal pockets of PI3K alpha simultaneously, separately, or sequentially. In some aspects of the disclosed methods, PI3K [alpha] inhibitors may target an allosteric or normal pocket of a PI3K [alpha] mutant that is resistant to treatment with another PI3K [alpha] inhibitor that targets a different pocket of PI3K [alpha].