80 results about "Phosphoinositide 3-kinase" patented technology

The invention relates generally to methods for inhibiting angiogenesis. More particularly, methods for inhibiting angiogenesis comprise selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in endothelial cells. The methods may comprise administration of one or more cytotoxic therapies including but not limited to radiation, chemotherapeutic agents, photodynamic therapies, radiofrequency ablation, anti-angiogenic agents, and combinations thereof.

The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine-, pyrimidine- and pyridine-based compoundŝ Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds; either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders mediated by lipid kinases. •Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. (Formula I)

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8 or 10 mg/kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The invention discloses a phosphoinositide 3-kinase (P13K) inhibitor, a pharmaceutical composition containing the P13K inhibitor, and application of the P13K inhibitor and the pharmaceutical composition. The P13K inhibitor comprises a pyrimidine compound and a stereoisomer/hydrate/pharmaceutically-acceptable salt thereof. The pyrimidine compound has a general formula I of which the structure is shown in the specification. The P13K inhibitor and the pharmaceutical composition containing the same can be used for inhibiting PI3 Ks and treating proliferative diseases on which the PI3 Ks act. According to the invention, high-effectiveness and high-selectivity inhibitors for treating proliferative diseases on which PI3Ks act can be provided.

Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure:

The invention discloses a liquid phase chip for detecting PIK3CA (phosphoinositide-3-kinase, catalytic, alpha) gene mutation. The liquid phase chip mainly comprises (A) a wild-type and mutant-type allele specific primer extension (ASPE) primer pair designed for mutational sites of a PIK3CA gene respectively, microspheres which are respectively coated with specific anti-tag sequences and have different colors of codes and amplification primers for respectively amplifying the target sequences of the PIK3CA gene with the corresponding mutational sites of the Exon 9 and/or Exon 20, wherein the anti-tag sequences can correspondingly complement and form pair with the selected tag sequences. The liquid phase chip has the following advantages: the coincidence rate of the detection method provided by the invention and a sequencing method is as high as 100%; the prepared liquid phase chip has very good signal to noise ratio; cross reactions do not exist between the designed probes and the anti-tag sequences; and parallel detection of various mutant types and various mutational sites on the same site can be realized.

Compounds of formula (I), defined herein, inhibit phosphoinositide 3-kinases (PI3K) and are useful for the treatment of disorders associated with PI3K enzymes.

The invention discloses a condensed heteroaryl derivative, and a preparation method and application thereof. The derivative disclosed by the invention is a phosphoinositide 3-kinase (PI3K) inhibitor which has the good inhabitation effect of the PI3K and the effect of inhibiting proliferation of cancer cells, so that the derivative can be used as a therapeutical agent for treating tumor.

In some embodiments, the invention includes a therapeutic combination 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, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-δ inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Compounds of formula 1 are effective modulators of PI3 kinase:

• • wherein R₁ is H, hydroxy, amino, lower alkyl, or trihalomethyl;
  • R₂ is amino, lower alkylamino, lower acylamino, arylamino, arylacyl-amino, heteroaryl-amino, heteroaryl-acyl amino, where aryl and heteroaryl are substituted with 0-3 substituents selected from the group consisting of halo, trihalomethyl, hydroxy, lower alkyl and lower alkoxy, or a substituent of the form —(CH₂)_n—C(═X)—R₈, where n is 014 3 inclusive and X is O or NR₉, where R₉ is H, lower alkyl, or R₁ and R₂ together form —CH═N—X— where X is CH, NH, O, or S, and R₈ is H, lower alkyl, lower alkoxy, aryl, aralkyl, or —(CH₂)_mCR₁₀R₁₁R₁₂, where m is 0-3 inclusive, and R₁₀, R₁₁, and R₁₂ are each independently H, lower alkyl, aryl, aralkyl, hydroxy, lower alkoxy, aryloxy, aralkoxy, amino, lower alkyl-amino, arylamino, aralkylamino, heteroaryl amino, or heteroaralkyl amino, where aryl and heteroaryl are substituted with 0-3 substituents selected from the group consisting of halo, hydroxy, and lower alkyl;
  • R₃ is H or lower alkyl; and
  • R₄, R₅, R₆, R₇ are each independently H, halo, hydroxy, amino, nitro, lower alkyl, or lower alkoxy;
  • and pharmaceutically acceptable salts thereof.

The invention provides a compound of Formula I,

Pharmaceutical compositions comprising such compounds and the use of such compounds in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The present invention provides bicyclic azaheterocyclobenzylamines of Formula I:

wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

The present disclosure relates to methods of treating a vascular malformation in a subject expressing a gain-of-function mutation in a PIK3CA gene comprising administering, to the subject, an effective amount of an agent that inhibits phosphoinositide 3-kinase (“PI3K”).

The present invention provides methods of inhibiting mast cell activity by administering a selective inhibitor of phosphoinositide 3-kinase delta (P13Kdelta). The invention also provides methods for treating or preventing a condition associated with undesirable mast cell activity in an individual comprising administering an effective amount of a selective P13Kdelta inhibitor.

The invention provides quinazoline heterocyclic compounds as well as a preparation method and an application thereof and belongs to the field of medicinal chemistry. The structural formula is shown as a formula (I) in the specification, wherein R<1> represents -H and -CH3; R<2> is defined in the specification, 8,10-dichloro-2,3-dihydro-[1,4] dioxane [2,3-f] quinazoline (IX) is prepared firstly, and then R<1> and R<2> substitution are performed. The compounds can be applied as PI3K (phosphoinositide 3-kinase) inhibitors for treating cancer.