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158 results about "Hypoxia-inducible factors" patented technology

Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia.

Stabilization of hypoxia inducible factor (HIF) alpha

The present invention relates to methods of stabilizing the alpha subunit of hypoxia inducible factor (HIF). The invention further relates to methods of preventing, pretreating, or treating conditions associated with HIF, including ischemic and hypoxic conditions. Compounds for use in these methods are also provided.
Owner:FIBROGEN INC

Oligomeric compounds for the modulation HIF-1α expression

Oligonucleotides directed against the hypoxia-inducible factor-1α (HIF-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.
Owner:ROCHE INNOVATION CENT COPENHAGEN

Method for preparing isoquinoline compounds

The invention relates to a method for preparing isoquinoline compounds and intermediate compounds obtained thereby. Such compounds can be used for preparing compounds and compositions which can reduce the activity of HIF hydroxylase enzyme, thereby improving the stability and / or activity of hypoxia inducible factors (HIF).
Owner:FIBROGEN (CHINA) MEDICAL TECHNOLOGY DEVELOPMENT CO LTD

RNA INTERFERENCE MEDIATED INHIBITION OF HYPOXIA INDUCIBLE FACTOR 1 (HIF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)

This invention relates to compounds, compositions, and methods useful for modulating hypoxia inducible factor (e.g., HIF1) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of HIF1 gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of HIF1 genes.
Owner:SIRNA THERAPEUTICS INC

Methods for providing neuroprotection for the animal central nervous system against the effects of ischemia, neurodegeneration, trauma, and metal poisoning

Methods and pharmaceutical compositions for preconditioning and / or providing neuroprotection to the animal central nervous system against the effects of ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease or stroke or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and / or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). Intranasal administration of DFO is known to stimulate and / or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia. Moreover, DFO is shown to decrease weight loss in subjects when administered pre and / or post stroke.
Owner:HEALTHPARTNERS RESEACH FOUND

Interaction between the VHL tumor suppressor and hypoxia inducible factor, and assay methods relating thereto

InactiveUS6787326B1Peptide/protein ingredientsAntibody mimetics/scaffoldsSuppressorTumour suppressor protein
The invention relates to the finding that the VHL tumour suppressor protein regulates hypoxia inducible factor alpha subunits, by targeting HIF alpha for destruction in normoxic, but not hypoxic cells. The invention provides assays for modulators of this interaction, and peptides based upon HIF alpha subunit sequence which may modulate this interaction.
Owner:OXFORD UNIV INNOVATION LTD

RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA)

This invention relates to compounds, compositions, and methods useful for modulating hyproxia inducable factor (e.g., HIF1) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of HIF1 gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of HIF1 genes.
Owner:SIRNA THERAPEUTICS INC

Methods and pharmaceutical compositions for differentially altering gene expression to provide neuroprotection for the animal central nervous system against the effects of ischemia, neurodegeneration, trauma and metal poisoning

ActiveUS20070092500A1Preventing and minimizing and treating neurologic complicationAvoid side effectsOrganic active ingredientsBiocideAntioxidantNose
Methods and pharmaceutical compositions for preconditioning and / or providing neuroprotection to the animal central nervous system against the effects of neurological disorders involving ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and / or stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. In another embodiment, the method is accomplished by differentially reducing, inhibiting or preventing the increased expression of selected genes caused by neurological disorders. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease, Huntington's disease, thalassemia or stroke, or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and / or copper such as iron chelators, copper chelators, and antioxidants. Particular examples of such therapeutic agents are the iron chelators deferoxamine (DFO) and deferasirox. Intranasal administration of DFO is known to stimulate and / or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia.
Owner:HEALTHPARTNERS RESEACH FOUND

Treatment of rheumatoid arthritis with hypoxia inducible factor-1alpha antagonists

The invention encompasses a novel method of treating inflammatory disease, such as rheumatoid arthritis, and novel methods of identifying and screening for drugs useful in the treatment of inflammatory diseases and their clinical symptoms. The inventors have made the discovery that the activity of HIF-1α, a transcription regulator known to have an effect on some cancers, has a significant impact on the pathophysiology of rheumatoid arthritis. The symptoms of an inflammatory disease, such as rheumatoid arthritis, may be alleviated by administering a compound that inhibits the activity of HIF-1α.
Owner:ENTELOS INC

Screening systems utilizing RTP801

RTP801 represents a unique gene target for hypoxia-inducible factor-1 (HIF-1). Down-regulation of the mTOR pathway activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of RTP801. The present invention relates to screening systems utilizing RTP801 and / or RTP801 interactors and / or RTP801 biological activity, to drug candidates identified by such screening systems, and to the use of such drug candidates in the treatment of various disorders.
Owner:QUARK FARMACUITIKALS INC

Methods for providing neuroprotection for the animal central nervous system against neurodegeneration caused by ischemia

Methods and pharmaceutical compositions for preconditioning and / or providing neuroprotection to the animal central nervous system against the effects of ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease or stroke or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and / or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). Intranasal administration of DFO is known to stimulate and / or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia. Moreover, DFO is shown to decrease weight loss in subjects when administered pre and / or post stroke.
Owner:HEALTHPARTNERS RESEACH FOUND

Process for making isoquinoline compounds

The present invention relates to methods for making isoquinoline compounds and the intermediate compounds achieved thereby. Such compounds can be used to prepare compounds and compositions capable of decreasing HIF hydroxylase enzyme activity, thereby increasing the stability and / or activity of hypoxia inducible factor (HIF).
Owner:FIBROGEN INC

RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA)

This invention relates to compounds, compositions, and methods useful for modulating hypoxia inducible factor (e.g., HIF1) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of HIF1 gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of HIF1 genes.
Owner:SIRNA THERAPEUTICS INC

Enhancing treatment of cancer and HIF-1 mediated disorders with adenosine A3 receptor antagonists

InactiveUS20060204502A1High activitySustained cellular protection against ischemiaOrganic active ingredientsBiocideDiseaseOncology
The present invention relates to the use of adenosine receptor antagonists, preferably A3 receptor antagonists, either alone or in combination with other agents for the treatment, prevention and / or management of diseases or disorders associated with overexpression of HIF-1α and / or increased HIF-1α activity (e.g., cancer, respiratory disease). The methods and compositions of the invention are particularly useful for preventing, treating, or ameliorating symptoms associated with a cancer, disease or disorder associated with hypoxia-inducible factor 1α (HIF-1α) using the A3 receptor antagonists of the invention. The present invention provides methods to inhibit the growth of tumors, particularly solid tumors and more particularly hypoxic tumors.
Owner:KING PHARMA RES & DEV

Isolated myeloid-like cell populations and methods of treatment therewith

InactiveUS20070231306A1BiocideSenses disorderCD33Mammal
The present invention provides an isolated myeloid-like cell population comprising a majority of cells that are lineage negative, and which express both CD44 antigen, CD11b antigen, and hypoxia inducible factor 1α (HIF-1α). These cells have beneficial vasculotrophic and neurotrophic activity when intraocularly administered to the eye of a mammal, particularly a mammal suffering from an ocular degenerative disease. The myeloid-like cells are isolated by treating bone marrow cells, peripheral blood cells or umbilical cord cells with an antibody against CD44 (hyaluronic acid receptor), against CD11b, CD14, CD33, or against a combination thereof and using flow cytometry to positively select CD44 and / or CD11b expressing cells therefrom. The isolated myeloid-like bone marrow cells of the invention can be transfected with a gene encoding a therapeutically useful protein, for delivering the gene to the retina.
Owner:THE SCRIPPS RES INST

Human hypoxia inducible factor-1 alpha recombinant adenovirus carrier and uses thereof

The invention relates to a mutant hypoxia inducible factor 1alpha, coded nucleic acid of the mutant hypoxia inducible factor 1alpha, a carrier containing wild coded nucleic acid of the mutant hypoxia inducible factor 1alpha, in particular to a recombinant adenovirus carrier and a drug composition containing the mutant hypoxia inducible factor 1 alpha, the coded nucleic acid and the carriers. The mutant protein, the nucleic acid, the carriers and the drug composition can be used to treat ischemic diseases, such as coronary heart disease, peripheral arterial ischemic vascular diseases, intermittent claudication and so on.
Owner:NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV

Process for preparing isoquinoline compounds

The present invention relates to a process for the preparation of isoquinoline compounds and intermediate compounds obtained therefrom. Such compounds can be used to prepare compounds and compositions that reduce the enzymatic activity of HIF hydroxylase, thereby increasing the stability and / or activity of hypoxia-inducible factor (HIF).
Owner:FIBROGEN (CHINA) MEDICAL TECHNOLOGY DEVELOPMENT CO LTD

Apigenin for chemoprevention, and chemotherapy combined with therapeutic reagents

InactiveUS20060189680A1Improved cancer therapyInhibit angiogenesisBiocideAnimal repellantsApigeninApoptosis
Apigenin is a nontoxic compound. The present invention is appropriate for apigenin use in people who have a high risk of getting cancer, and in people who have cancer through chemoprevention and chemotherapy, respectively. We showed that apigenin inhibited cancer cell proliferation, tumor growth and angiogenesis. Apigenin selectively inhibited proliferation and induced apoptosis of cancer cells, enhanced the sensitivity of different cancer cells to different therapeutic drugs including cisplatin and taxol. Apigenin also inhibits angiogenesis and tumor growth in human cancers, and inhibits angiogenic inducers such as hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF). Apigenin inhibited expression of HIF-1 and VEGF through PI3K, AKT, p70S6K1 and HDM2 pathways, which are commonly observed in all kinds of human cancers. Thus, our results indicate that apigenin can be applied to various human cancers for chemoprevention, and for chemotherapy when combined with other therapeutic reagents.
Owner:ACC THERAPEUTICS

Uses of hypoxia-inducible factor inhibitors

The present invention relates to treating a hematologic cancer using a Hypoxia- Inducible Factor (HIF inhibitor). The invention also relates to inducing acute myeloid leukemia remission using the HIF inhibitor. The invention further relates to inhibiting a maintenance or survival function of a cancer stem cell (CSC) using the HIF inhibitor.
Owner:ONCOC4 INC

Screening systems utilizing RTP801L

InactiveUS20080014599A1Inhibit and enhance activityCompound screeningApoptosis detectionUnique geneMRNA synthesis
RTP801L represents a unique gene target for hypoxia-inducible factor-1 (HIF-1) that may regulate hypoxia-induced pathogenesis; down-regulation of the mTOR pathway activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of RTP801L.The present invention relates to screening systems utilizing RTP801L and / or RTP801L interactors and / or RTP801L biological activity, and to the potential drugs and methods of treatment identified by such screening systems.
Owner:QUARK FARMACUITIKALS INC

Method of treating Alzheimer's disease comprising administering deferoxamine (DFO) to the upper one-third of the nasal cavity

ActiveUS7776312B2Avoid side effectsStimulate and stabilize HIF-1αBiocideOrganic active ingredientsNervous systemNose
Methods and pharmaceutical compositions for preconditioning and / or providing neuroprotection to the animal central nervous system against the effects of neurological disorders involving ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and / or stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. In another embodiment, the method is accomplished by differentially reducing, inhibiting or preventing the increased expression of selected genes caused by neurological disorders. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease, Huntington's disease, thalassemia or stroke, or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and / or copper such as iron chelators, copper chelators, and antioxidants. Particular examples of such therapeutic agents are the iron chelators deferoxamine (DFO) and deferasirox. Intranasal administration of DFO is known to stimulate and / or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia.
Owner:HEALTHPARTNERS RESEACH FOUND

Regulation of HIF protein levels via deubiquitination pathway

The hypoxia inducible factor-1 (HIF-1) transcription factor is an important regulator of the cellular response to hypoxia. The activity of HIF-1 is regulated by the level of the HIF-1α subunit, HIF-1α, which is rapidly degraded under normoxic conditions by the ubiquitin-proteasome pathway. HIF-1α levels increase under hypoxic conditions. Many human cancers also show constitutively increased HIF-1α levels. PX-478 or S-2-amino-3-[4′-N,N,-bis(2-chloroethyl)amino]phenyl propionic acid N-oxide dihydrochloride, is a novel anticancer agent, and is capably of decreasing both constitutive and hypoxia induced HIF-1α protein levels and HIF-1 transactivation in vitro and in vivo. In method embodiments, the administration of PX-478 is independent of the pathways of HIF-1α regulation involving the von Hippel-Lindau protein and p53. PX-478 causes an increase in polyubiquitinated HIF-1α levels due to inhibition of HIF-1α deubiquitination. The levels of other proteins whose proteasomal breakdown is mediated by ubiquitination are not affected by PX-478. Deubiquitination is a novel pathway for the regulation of cellular HIF-1α levels and PX-478 is a specific inhibitor of the pathway. Therapeutic compounds for regulating cellular HIF-1α levels and methods of regulating cellular HIF-1α levels are herein provided.
Owner:PROLX PHARMA +1
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