85 results about "Phosphoinositide 3-kinase" patented technology

The invention relates generally to methods for treating and / or preventing aberrant proliferation of hematopoietic cells. More particularly, the invention relates to methods for treating and / or preventing aberrant proliferation of hematopoietic cells comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in hematopoietic cells. The methods may be used to treat any indication involving aberrant proliferation of hematopoietic cells.

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 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 compounds^ 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.; DEG 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.

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.

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 compounds^ 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.

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 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 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 treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

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.

The present invention generally relates to pharmacology and, in particular, to the treatment of tumors and other conditions. In some aspects, the invention is directed to the treatment of subjects having tumors or cancers that are metastatic. Surprisingly, it has been found that certain compositions comprising oxidized glutathione-based compounds are able to effectively treat such cancers by inhibiting cell migration and / or invasion processes, and thus, inhibiting tumor cell metastases. Without being bound by any theory, it is believed that such compositions are effective since the compositions are able to suppress the activation of critical signaling pathways within cells that are used for cell migration, such as the ErbB2 and / or phosphoinositide-3 kinase (PI3K) pathways, including the downstream RhoA and AKT pathways. Such pathways are regulated by ERp5, which is a protein disulfide isomerase regulated using certain redox pathways, and those redox pathways are unusually sensitive to treatment using oxidized glutathione-based compounds. Thus, the composition of the instant invention, in some embodiments, are surprisingly effective at preventing tumor metastases. While other references have disclosed the treatment of cancers using oxidized glutathione-based compounds, no reference has suggested that signaling pathways used for cell migration, invasion and metastasis, such as the ErbB2, PI3K, RhoA, and AKT pathways, are highly susceptible to treatment by altering the redox state of the cell, e.g., by oxidized glutathione-based compounds. Accordingly, the use of such compositions to treat tumor metastases is surprising and could not be predicted given the teachings of the prior art.

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 invention relates to new triazines (G = Q = U are N), pyrimidines (two out of G, Q and U are N), and pyridopyrimidines (one of G and U together with R2 forms an anullated pyridine ring) of formula (I) carrying a spirocyclic substituent, wherein E1 is CR4 or N; X1 is CHR4, CH2CH2, NR4, NR4?0, or O; and the other substituents are as defined in the specification. The compounds inhibit phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), DNA-PK and ATM kinase, and may be used as therapeutic agents or diagnostic probes. The invention also relates to methods of using the compounds for treatment of associated pathological conditions.

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.

The present invention relates to pyridine methylene azolidinone compounds of Formula (I)for the treatment and / or prophylaxis of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, allergy, asthma, pancreatitis, multi-organ failure, kidney diseases, platelet aggregation, cancer, sperm motility, graft rejection or lung injuries. Specifically, the present invention is related to pyridine methylene azolidinone derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide-3-kinases, PI3Ks.

The present invention relates to selective inhibitors of phosphoinositide (PI) 3-kinase β, use of the selective inhibitors in anti-thrombotic therapy, and a method for screening compounds useful for the new anti-thrombotic therapy by detecting selective inhibitory activity of PI 3-kinase β of the compound. The invention also relates to novel compounds that are inhibitors of PI 3-kinase.

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; andR4, 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 relates to a selective depressant of phosphoinositide (PI) 3-kinase Beta, which is applied to the anti-thrombosis therapy, and a method of screening a compound used by a novel anti-thrombosis therapy by detecting the selective inhibitory activity of the PI 3-kinase Beta of the compound.

The invention relates to novel phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor compounds of formula (I) and (II), which are conformationally restricted, and for which the meaning of the substituents are listed in the description. Preferred compounds are those wherein X isoxygen, R1 is morpholino and R2 is substituted phenyl or heteroaryl. These compounds are useful, either alone or in combination with further therapeutic agents, for treating disorders mediated by lipid kinases.