277 results about "Discovery and development of mTOR inhibitors" patented technology

Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

An implantable catheter or shunt for draining fluid from a body cavity. The catheter or shunt body has a wall structure that carries one or more therapeutic agents in a manner enabling release of the therapeutic agent from the wall structure in situ after surgical implantation of the catheter or shunt body. The therapeutic agent can be gradually released over time to prevent infection, inhibit tissue ingrowths, and / or provide some other desired medicinal purpose. As an example, the therapeutic agent can be rapamycin or an mTOR inhibitor. According to some contemplated embodiments of the present invention, the therapeutic agent carried by the catheter / shunt is rechargeable or refillable in situ so that the therapeutic agent can be gradually released from the catheter / shunt over the expected useful life of the catheter / shunt.

The invention features methods and compositions including an mTOR inhibitor and a tyrosine kinase inhibitor for reducing the proliferation of and enhancing the apoptosis of neoplastic cells. The addition of an MEK inhibitor to this combination further enhances the effectiveness of this therapeutic method.

A combination of temsirolimus and herceptin in the treatment of cancer is provided. A combination of temsirolimus and HKI-272 is provided. A combination of herceptin and HKI-272 is also provided. Regimens and kits for treatment of metastatic breast cancer, containing herceptin, temsirolimus and / or HKI-272, optionally in combination with other anti-neoplastic agents, or immune modulators are described.

The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

The invention which belongs to the technical field of medicines concretely relates to tricyclic dual PI3K and mTOR inhibitors with a general formula represented by formula (I), pharmaceutically acceptable salts thereof, or stereoisomers thereof. In the formula (I), R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, X, A, and B are defined in the specification. The invention also relates to a preparation method of above compounds, a medicinal preparation containing the compounds, and an application of the compounds in the preparation of medicines for treating and / or preventing proliferative diseases responding to the inhibition of the activity of lipase and / or PI3-kinase-related protein kinase, especially the PI3 kinase and / or mTOR.

Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

The present disclosure provides methods for using CD37-specific binding molecules (such as a CD37-specific SMIP or antibody) in combination with mTOR inhibitors (such as rapamycin and derivatives or analogues thereof) or phosphatidylinositol 3-kinase (PI3K) inhibitors (such as p110δ-specific inhibitors or the like), which can be done concurrently or sequentially, to treat or prevent a B-cell related hyperproliferative disease, such as a lymphoma, carcinoma, myeloma, or the like.

The present invention relates to compositions and methods for the detecting, preventing, treating, and empirically investigating seizures and seizure related disorders (e.g., West syndrome, TSC, childhood absence epilepsy, benign focal epilepsies of childhood, juvenile myoclonic epilepsy (JME), temperol lobe epilepsy, frontal lobe epilepsy, Lennox-Gastaut syndrome, occipital lobe epilepsy). In particular, the present invention provides compositions and methods for detecting, treating, preventing and empirical investigating seizures and seizure related disorders through inhibition of mTOR function. In addition, the present invention provides methods and compositions that utilize mTOR inhibiting agents (e.g., rapamycin) in the detecting, preventing, treating, and empirical investigating of seizures and seizure related disorders.

The invention relates, in part, to a method of treating a subject comprising administering to the subject a low, immune enhancing of a mTOR inhibitor and an immune effector cell engineered to express a CAR.

The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

The present invention relates to Imidazolopyrimidine Analogs, methods of making Imidazolopyrimidine Analogs, compositions comprising an Imidazolopyrimidine Analog, and methods for treating or preventing a PI3K-related disorder comprising administering to a subject in need thereof an effective amount of an Imidazolopyrimidine Analog. The invention also relates to methods for treating or preventing mTOR-related disorders comprising administering to a subject in need thereof an effective amount of an Imidazolopyrimidine Analog.

Provided herein is a combination therapy comprising a JAK kinase inhibitor and a dual PI3K / mTOR inhibitor, as well as methods of treating various cancers through the use of such a combination therapy.

Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM, leading to widespread shutdown of vascular flow, hemorrhage, and necrosis. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and / or mTOR inhibitors.

The present invention provides methods and compositions for treating bladder cancer, including metastatic bladder cancer and non-muscle-invasive bladder cancer, by administering a composition comprising nanoparticles that comprise mTOR inhibitor and optionally an albumin.

The present application demonstrates that HDAC inhibitors can be used in combination with hormonal therapy to treat and prevent estrogen receptor positive breast cancer. HDAC inhibitors can also be combined with IGF-1R inhibitors, mTOR inhibitors, and EGFR inhibitors to treat breast cancer, optionally in combination with hormonal therapy if indicated. Combinations of the compounds, with or without HDAC inhibitors, and with or without hormonal therapy, can also be used. The invention therefore provides methods of treatment and pharmaceutical compositions.

The invention provides the use of a combination of an mTOR inhibitor and capecitabine in the treatment of cancer.

Provided are compositions and methods for enhancing immune responses to an antigen. The compositions contain an isolated population of CD8+T cells and an inhibitor of mammalian target of rapamycin (mTOR). The method for obtaining an enhanced immune response to an antigen in an individual entails administering to the individual the antigen and an inhibitor of mammalian target of rapamycin (mTOR). CD8+T cells may also be used for adoptive cell transfer (ACT) therapy.

The present invention relates generally to novel compounds relating to the diagnosis and treatment of pathologies relating to the Hedgehog pathway, including but not limited to tumor formation, cancer, neoplasia, and non-malignant hyperproliferative disorders. The present invention includes novel compounds, novel compositions, methods of their use and methods of their manufacture, where such compounds are generally pharmacologically useful as agents in therapies whose mechanism of action involve methods of inhibiting tumorigenesis, tumor growth and tumor survival using agents that inhibit the Hedgehog and Smo signaling pathway.

The present invention discloses methods of using of compounds for the enhancement of the innate immune system of a patient. In particular, the active compounds of the present invention include at least one calcineurin inhibitor, mTOR inhibitor or non-immunosuppresive derivative, or a derivative, isomer, or pharmaceutically acceptable salt thereof; and optionally, at least one calciferol or LMW inhibitor, or a derivative, isomer, or pharmaceutically acceptable salt thereof. Pharmaceutical formulations comprising same are also disclosed.

Compounds of formula Iwherein:R1 isand R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

The present invention relates to compositions containing an mTOR inhibitor, such as rapamycin or a rapamycin derivative, in combination with a PI3 kinase inhibitor and / or a leptin inhibitor, intraluminal devices configured to release such compositions, and methods for the treatment and / or prevention of intimal hyperplasia, vascular stenosis and / or restenosis comprising delivery of such compositions or intraluminal devices to subjects in need thereof. The compositions, intraluminal devices, and methods of the invention are particularly well-suited for the treatment or prevention of vascular stenosis and restenosis in obese and diabetic subjects.

Disclosed are methods for treating a patient with an mTOR inhibitor such as AP23573, sirolimus, temsirolimus, everolimus, etc.

An apparatus and method of preparing a cardiac harness for use in controllably delivering a medicament such as an mTOR inhibitor or aldosterone blockade from the surface of the cardiac harness to the epicardium of a patient's heart for the site-specific treatment of cardiac and non-cardiac maladies. The delivery of the medicament from the cardiac harness is achieved by: coating the medicament on the surface of the cardiac harness; coating the cardiac harness with a polymer material or dielectric material and impregnating the coating with the medicament; or by loading the medicament into an implant attached to the cardiac harness.