52 results about "Phosphoinositide 3-kinase inhibitor" patented technology

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.

Compounds of Formulas Ia and Ib, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib 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 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.

Disclosed is an anti-cancer drugs slow release agent containing Epothilone which comprises slow release microspheres and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active constituents include Epothilone, Epothilone derivatives, Epothilone B, Epothilone D and combination of anti-cancer drugs selected from phosphoinositide-3-kinase inhibitor, of pyrimidine analogues and / or DNA restoring enzyme inhibitor, the slow release auxiliary materials include polylactic acid and its copolymer, polyethylene glycol, PLA-COOH copolymer, di-aliphatic acid and sebacylic acid copolymer, poly(erucic aciddipolymer-sebacylic acid), poly(fumaric acid-sebacylic acid), Polifeprosan, polylactic acid and other biocompatible high polymers, the viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose. The anticancer active constituents and the slow release microspheres can also be prepared into slow release implanting agent for intra-tumor or around-tumor injection or placement for the effective suppression of tumor growth and for the appreciable enhancement for curative effects of non-operative treatments such as chemotherapy.

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 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 provides an anti-cancer sustained-release agent co-carrying glucocorticoid and chemotherapeutic drugs and belongs to sustained-release injections. The anti-cancer sustained-release agent comprises sustained-release microspheres and a solvent, wherein, the sustained-release microspheres comprise anti-cancer active components and sustained-release auxiliary materials; and the solvent is a particular solvent containing a suspending agent. The glucocorticoid is selected from prednisolone, methylprednisolone, dexamethasone, betemethasone, triamcinolone acetonide or triamcinolone acetonide; the chemotherapeutic drugs are selected from phosphoinositide 3-kinase inhibitor, pyrimidine analogues and the like; the sustained-release auxiliary materials are biocompatible high-polymers, such as polylactic acid and the copolymers thereof, polyethylene glycol, carboxyl-terminated polylactic acid copolymers, polyfatty acid dimer-sebacic acid copolymers, poly(erucic acid dimer-sebacic acid), poly(fumaric-co-sebacic acid), polifeprosan and the like; and the suspending agent with the viscosity being 100cp to 3,000cp (at the temperature of 20 to 30 DEG C) is selected from sodium carboxymethyl cellulose and the like. The anti-cancer active components and the sustained-release microspheres can further be prepared into sustained-release implants which can effectively inhibit the growth of tumors, alleviate edema and improve the curative effects of radiotherapy and chemotherapy by intra-tumor or peri-tumor injection or placement.

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 an anti-cancer drug slow release injection containing gemcitabine, which comprises slow release microspheres and a menstruum, wherein the microsphere comprises anti-cancer active ingredients and slow release auxiliary materials, and the menstruum is a special menstruum containing a suspending agent; the anti-cancer active ingredients are gemcitabine, or antimetabolites selected from zalcitabine, emtricitabine, galocitabine, ibacitabine, ancitabine, decitabine, flurocitabine, enocitabine, imidazole gemcitabine, capecitabine, gemcitabine, fludarabine or cladribine, and / or antimetabolite potentiating agents selected from phosphoinositide 3-kinase inhibitor, pyrimidine analogue and / or DNA repair enzyme inhibitor; the slow release auxiliary materials are polifeprosan, dienoic fatty acid, decanedioic acid copolymer, polylactic acid copolymer, EVAc and the like; the suspending agent has a viscosity of 100cp-3000cp (20-30 DEG C), and is selected from sodium carboxymethylcellulose and the like. The slow release microspheres can be prepared into slow release implants. When injected or placed into tumors or at peripheries of tumors, the slow release microspheres can enhance the treatment effect of non-operative treatment methods, such as radiotherapy, chemotherapy, etc.

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”).

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 6 Pt compounds including bicycloplatinum, etc and 3 cytotoxins including phosphoinositide 3-kinase inhibitor, pyrimidine analog or DNA repairase inhibitor, and the slow-release auxiliary.

The anticancer composition containing tyrosine kinase inhibitor is slow released injection and slow released implanted preparation. Its effective anticancer component is the composition of Erbitux, Iressa, Tarceva, Sunitinib, Trastuzumab and other tyrosine kinase inhibitor, and Edelfosine, miltefosine, perifosine, ilmofosine and other phosphoinositide-3-kinase inhibitor. Its slow releasing supplementary material is selected from p(LAEG-EOP), p(DAPG-EOP), other polyphosphate copolymer, poly(erucic acid dipolymer-sebacic acid), etc. The anticancer composition may injected or set into tumor and can maintain the effective medicine concentration for over 50 days with obviously reduced general reaction and capacity of raising the treating effect of chemotherapeutic and / or radiotherapeutic medicine.

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 13 antimetabolic medicines including gemcitabine, zalcitabine, etc and 3 cytotoxins including phosphoinositide 3-kinase inhibitor, pyrimidine analog or DNA repairase inhibitor, and the slow-release auxiliary.

A anticarcinogenic slow release injection carrying platinum compounds and a synergist thereof is composed of slow release microspheres and a dissolvant, wherein, the slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active component comprises platinum compounds such as sunpla, dicycloplatin, eptaplatin, (cis-amminedichloro(2-methylpyridine) platinum, camphoramine chloroacetic platinum or picoplatin, and the like, and a cytotoxic drug selected from a phosphoinositide 3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecules such as polylactic acid and copolymer thereof, polyethylene glycol, carboxyl end polylactic acid copolymer, copolymer of dienoic fatty acid and sebacic acid, poly (erucic acid dimer-sebacic acid), poly (fumaric acid-sebacic acid), polifeprosan, polylactic acid, EVAc, and the like, and the suspending agent has the viscosity of 100cp-3,000cp (at the temperature of 20-30 DEG C) and is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can also be made into a slow release implant. The slow release injection is injected or placed in tumors or around the tumors, which can improve the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like.

An anticarcinogenic slow release injection carrying an angiogenesis inhibitor and a synergist thereof is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active components are angiogenesis inhibitors such as gefitinib, erlotinib, lapatinib, vatalanib, pelitinib, thalidomide, ranolamine, angiostatin, endostatin, imatinib, thalidomide, ranolamine, simatinib, dasatinib, avastin, kanatini, sorafenib, sunitinib, telstar or panitoma, and the like, and / or cytotoxic drugs selected from a phosphoinositide-3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecule; the viscosity of the suspending agent is 100cp-3,000cp (at the temperature of 20-30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can be also made into a slow release implant, and the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like, can be improved when the slow release injection is injected or placed in tumors or around the tumors.

The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and / or uncoupling protein 1 (Thermogenin / Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

The present invention is directed to a formulation for treating cancer comprising an androgen receptor signaling inhibitor and a B-cell-lymphoma-2 inhibitor, which may further comprising a Bromodomain-and-Extra-Terminal protein inhibitor or a phosphoinositide 3-kinase inhibitor.

The invention relates to cancer therapy drug sustained-release injection containing gemcitabine. The injection comprises sustained-release microspheres and dissolvent, wherein, the sustained-release microspheres comprise active ingredients for cancer therapy and sustained-release auxiliary materials, and the dissolvent is special dissolvent containing suspending agent. The active ingredients for cancer therapy comprise antimetabolite of gemcitabine or antimetabolite selected from zalcitabine, emtritabine, galocitabine, ibacitabine, ancitabine, decitabine, flurocitabine, enocitabine, imidazoletabine, capecitabine, gemcitabine, fludarabine or cladribine, and / or antimetabolite synergist selected from phosphoinositide 3-kinase inhibitor, pyrimidine analogs and / or DNA repair enzyme inhibitor; the sustained-release auxiliary materials comprise polifeprosan, bi-fatty acid, decanedioic copolymer, polylactic copolymer and EVAc; the viscocity of the suspending agent is 100cp to 3000cp (at 20 to 30 DEG C) and the suspending agent is selected from sodium carboxymethyl cellulose. The sustained-release microspheres can also be produced into sustained-release implant, and by injecting or positioning the sustained release agent in tumor or tumor margin, the efficacy of non-operative treatment such as radiation treatment and chemical treatment can be enhanced.

The invention discloses a slow-release formulation comprising taxoid and the potentiating agent, which comprises sustained release microsphere and solvent; wherein, the sustained release microsphere comprises effective anticancer component and sustained release accessories; the solvent is common solvent or special solvent comprising suspending agent; the effective anticancer component is divided into the taxoid or the potentiating agent of the the taxoid; the potentiating agent of the taxoid is selected from phosphoinositide 3-kinase inhibitor and pyrimidine analogue and / or DNA repair enzyme inhibitor; the sustained release accessories are selected from polylactic acid and the copolymer, ethylene-vinyl acetate copolymer, polifeprosan, di-fatty acid and sebacic acid copolymer, poly (erucic acid dimer - sebacic acid), poly (fumaric acid - sebacic acid) and other copolymers; the suspending agent is selected from sodium carboxymethyl cellulose and other substance; the sustained release microspheres also can be produced into sustained-release implant. The slow-release formulation has the advantages of lowering toxic reaction of whole body through injecting or arranging slow-release formulation into or around tumor, but also selectively improving partial drugs concentration for tumor and strengthening therapeutic effect of non-surgical therapy such as chemotherapy and radiotherapy.

An anticarcinogenic slow release injection carrying an angiogenesis inhibitor and a synergist thereof is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active components are angiogenesis inhibitors such as gefitinib, erlotinib, lapatinib, vatalanib, pelitinib, thalidomide, ranolamine, angiostatin, endostatin, imatinib, thalidomide, ranolamine, simatinib, dasatinib, avastin, kanatini, sorafenib, sunitinib, telstar or panitoma, and the like, and / or cytotoxic drugs selected from a phosphoinositide-3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecule; the viscosity of the suspending agent is 100cp-3,000cp (at the temperature of 20-30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can be also made into a slow release implant, and the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like, can be improved when the slow release injection is injected or placed in tumors or around the tumors.

The invention provides an anti-cancer medicine composition, which comprises anticancer active constituent and medicinal adjuvant, the anticancer active constituent employs phosphoinositide-3 and nitrosoureas, wherein the phosphoinositide-3 can effectively suppress the growth of the tumor cells, lower the survivability of tumor cells to Semustine anti-cancer drugs, and the medicinal adjuvant mainly employs biological compactable, degradable and absorbing, which can slowly release the phosphoinositide-3 kinase inhibitor onto tumor partially during the degradation and absorption process, thus the whole body toxicity reaction is reduced appreciably , and the effective medicinal concentration can be sustained to the tumor partially. The anti-cancer medicinal composition also contain Nitrosoureas anti-cancer drugs, when locally dispensed on the tumor, the composition can lower down the whole body toxicity reaction of the anti-cancer medicament, selectively increase the tumor local medicinal concentration, and the treatment effect of the non-operative treatment methods such as chemotherapy, medicament and radiation can be improved.

Disclosed is an anticancer medicinal injection and its use, which comprises slow release microspheres and dissolvent, the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being conventional dissolvent or specific dissolvent containing suspension adjuvant. The anticancer active constituents include anti-metabolism anti-cancer drugs, phosphoinositide-3-kinase inhibitor, DNA restoration enzyme inhibitor or CENUs, the suspending agent is selected from sodium carboxymethylcellulose and mannitol. The injection can lower down the whole body toxicity reaction of the anti-cancer medicament, selectively increase the tumor local medicinal concentration, and improve the treatment effect of the non-operative treatment methods such as chemotherapy, medicament and radiation.

The present invention relates to a anti-cancer slow-release preparation containing glucocorticoid and chemotherapeutic medicine. Said anti-cancer slow-release preparation is a slow-release injection formed from slow-release microsphere and solvent. The slow-release microsphere includes anti-cancer effective component and slow-release auxiliary material, its solvent is a special solvent containing suopension adjuvant. The glucocorticoid is selected from prednisolone, methyl prednisolone, dexamethasone, betamethasone, triamcinolone and triamcinolone acetonide, its chemotherapeutic medicine is selected from phosphoinositide 3-kinase inhibitor and pyrimidine analogues. The slow-release auxiliary material is polylactic acid and its copolymer, polyethylene glycol, carboxyl-terminated polylactic acid copolymer, difatty acid and sebacic acid copolymer, poly (erucidic acid dimer-sebacic acid) and poly (fumaric acid-sebacic acid) biological compatibility macromolecule, and the suspension adjuvant is selected from carboxymethylcellulose sodium, etc. Said invention also can be made into slow-release implantation preparation.

The present disclosure provides selective phosphoinositide 3-kinase inhibitors of formula (A), or pharmaceutically acceptable salts thereof. These compounds are useful for the treatment of conditions mediated by one or more P13K isoforms, such as PI3K delta (PI3Kδ). The present disclosure further provides methods of inhibiting phosphoinositide 3-kinase inhibitors using these compounds for treatment of disorders related to phosphatidylinositol 3-kinase activity.

The slow released compound anticancer injection containing bendamustine and its synergist consists of slow released microsphere and solvent. The slow released microsphere includes effective anticancer component and slow releasing supplementary material, and the solvent is special solvent containing suspending agent. The effective anticancer component is the composition of bendamustine and bendamustine synergist selected from phosphoinositide 3-kinase inhibitor, pyrimidine analog and DNA repairase inhibitor. The slow releasing supplementary material is polylactic acid and its copolymer, polifeprosan, EVAc or other biocompatible polymer. The .suspending agent is carboxymethyl cellulose, etc. and has viscosity of 100-3000 cp at 20-30 deg.c. The slow released microsphere may be also prepared into slow released implanting agent. The present invention can inhibit the growth of tumor and enhance the curative effect of chemotherapy, radiotherapy and other non-operative treatment.

An anti-cancer combination containing a phosphoinositide3-kinase inhibitor (PI3Ki) and / or a topoisomerase inhibitor is a sustained-release injection, which contains a sustained-release microsphere and a menstruum. The sustained-release microsphere contains PI3Ki and / or topoisomerase inhibitor and sustained-release auxiliary materials; the menstruum is an ordinary menstruum or a special menstruum containing a suspending agent. The viscosity of the suspending agent is 100cp to 3000cp (at the temperature of 20 DEG to 30 DEG) and the suspending agent is selected from carboxymethylcellulose sodium, etc. The sustained-release auxiliary materials are selected from a polyphosphonate copolymer of p(LAEG-EOP), p(DAPG-EOP), p(BHET-EOP / TC), p(BHET-EOP / TC ), p(BHDPT-EOP / TC), p(BHDPT-EOP / TC), p(CHDM-HOP) or p(CHDM-EOP), and the like, or a copolymer of polyphosphate ester and polylactic acid, polifeprosan, dienoic fatty acid or decanedioic acid, a copolymer or a mixture of p(erucic acid dimer-decanedioic acid) or a copolymer or a mixture of p(boletic acid-decanedioic acid). The anti-cancer combination is also made into a sustained-release implanting agent, which can be injected or placed in or around tumor to maintain the effective medicine density for more than 40 days. The anti-cancer combination can also obviously reduce the general reaction of the medicine and selectively enhance the curing effect of non-operational therapies such as radiotherapy and chemotherapy.