174 results about "NF-κB" patented technology

The use and screening of modulators of apoptosis is disclosed. The modulators may be, for example, modulator of NF-κB activity. The modulators may be used, for example, in the treatment of NF-κB-mediated diseases, conditions, and injuries.

Compounds that inhibit the activity of NF-κB or inhibit the activity of the proteasome or both promote bone formation and hair growth and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyrdidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation; they also stimulate the production of hair follicles and are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

The invention provides methods for the inhibition of inflammation by providing, to a cell, in need thereof, monoterpene compositions that inhibit NF-κB. These compositions may also contain a carrier moiety that renders the monoterpene composition membrane permeable. The carrier may include triterpenoid moieties, sugars, lipids, or even additional monoterpenoid moieties. The composition can also contain additional chemical functionalities. Methods for using these compounds to prevent and treat a wide range of inflammatory conditions, especially, premalignant inflammatory conditions are described.

The invention relates to the treatment multiple sclerosis, and in particular to the treatment of the inflammatory injury seen in the progressive stages in the disease such as seen with the recurrent upsurges of acute disease, classically known as “relapses” or “exacerbations” or “relapsing / remitting” disease seen in multiple sclerosis. The invention provides a method for modulating a relapsing / remitting disease in a subject suffering therefrom involving providing the subject with a gene-regulatory peptide or functional analogue thereof. Furthermore, the invention provides the use of an NF-κB down-regulating peptide or functional analogue thereof for the production of a pharmaceutical composition for the treatment of relapsing / remitting disease as seen with multiple sclerosis.

The invention involves the treatment, prevention, and reduction of immunoinflammatory disorders involving the combination of an agent that increases the signal activity of a glucocorticoid receptor (e.g., glucocorticoid receptor agonist) and an agent that modulates the signaling activity of one or more signaling pathways selected from the NF-κB pathway, NFAT pathway, AP-1 pathway, and Elk-1 pathway such that proinflammatory cytokine secretion or production, or any other inflammatory response, is reduced. Further, screening methods are provided for identifying candidate compounds and strategies useful for treating, preventing, or reducing such conditions.

Latent TGFβ induces constitutive activation of NF-κB but does not activate Smad signaling. Latent TGFβ may be used to identify modulators of signaling pathways that are essential for tumor maintenance. Latent TGFβ may also be used to protect a patient from treatments that induce apoptosis.

The use and screening of modulators of apoptosis is disclosed. The modulators may be, for example, modulator of NF-κB activity. The modulators may be used, for example, in the treatment of NF-κB-mediated diseases, conditions, and injuries.

It is intended to efficiently treat an inflammatory disease without causing side effects. This object can be achieved by providing a medicinal composition for treating and preventing an inflammatory disease and disorders, and disorders caused by the disease and disorders which contains at least one decoy of NF-κB or an analogous transcriptional factor and a pharmaceutically acceptable carrier; and a method of treating and preventing an inflammatory disease and disorders, and disorders caused by the disease and disorders which comprises the step of administering to a patient a composition containing at least one decoy of NF-κB or an analogous transcriptional factor and a pharmaceutically acceptable carrier.

Described herein are methods and compositions for inhibiting, treating and reversing intervertebral disc disorders using transcription factor inhibitors. In certain embodiments, the transcription factor inhibitor targets the transcription factor NF-κB. Also described are methods and compositions where intervertebral disc disorder is reversed using a decoy oligodeoxy-nucleotide that blocks NF-κB.

The present invention provides a RANK (receptor activator of NF-κB) inhibitor consisted of a TRAF-6 (TNF receptor-associated factor-6) binding domain attached to a leader sequence. The peptide inhibitor inhibits RANKL (RANK ligand)-mediated osteoclast differentiation, thus indicating that targeted disruption of interaction between RANK and TRAF6 may prove useful as a therapeutic for metabolic bone disorders, leukemia, arthritis, and metastatic cancer of the bone.

The present invention relates to new class of non-steroidal compounds which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity including obesity, diabetes, inflammatory- and immune-associated diseases, and have the structure including all stereoisomers thereof, tautomers thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein X is selected from N, O, and S; Y is N or CR6; Z is a ring; and where R, Ra, Rb, Rc, Rd, R1, R2, R3, R4, and R5 are as defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

The present invention provides markers associated with activated molecular signaling pathways (example: p38 MAKP, NF-κB, ERK1 / 2, YY-1 and AKT) inhibited by rituximab in cancer cells as well as pathways activated by rituximab (such as death receptors, RKIP, PTEN) all of which are associated with the regulation of chemo and immunoresistance. The present invention provides methods of prognosis and providing a prognosis for cancer such as lymphoma, leukemia, and autoimmune disease, as well as, methods of drug discovery. These markers are also therapeutic targets for treatment of cancer resistant to conventional and experimental cancer therapeutics. Inhibition or activation of expression and / or activity of targeted gene products sensitizes resistant tumor cells to subtoxic doses of cytotoxic treatment including chemotherapy, radiation therapy, or immunotherapy and gene therapy, and the cytotoxic molecules.

Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) its stereoisomers thereof, or a solvate thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, where Z is CONR1R2 or CH2NR1R2 and where R, R′, Ra, Rb, Rc, Rd, Z, A and B are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

The current invention provides novel thiomolybdate derivatives, methods of making novel thiomolybdate derivatives, pharmaceutical compositions of novel thiomolybdate derivatives, methods of using novel thiomolybdate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-κB dysregulation and methods of using pharmaceutical compositions of thiomolybdate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-κB dysregulation.

The present invention relates to tolerogenic mammalian dendritic cells (DCs) and methods for the production of the tolerogenic DCs. In addition, the present invention provides a method for enhancing tolerogenicity in a host comprising administering the tolerogenic mammalian DCs of the present invention to the host. The tolerogenic DCs of the present invention comprise an oligodeoxyribonucleotide (ODN) which has one or more NF-κB binding sites. The tolerogenic DCs of the present invention may further comprise a viral vector, and preferably an adenoviral vector, which does not affect the tolerogenicity of the tolerogenic DCs when present therein. Enhanced tolerogenicity in a host is useful for prolonging foreign graft survival and for treating inflammatory related diseases, such as autoimmune diseases.

Described herein are methods and compositions for inhibiting, treating and reversing intervertebral disc disorders using transcription factor inhibitors. In certain embodiments, the transcription factor inhibitor targets the transcription factor NF-κB. Also described are methods and compositions where intervertebral disc disorder is reversed using a decoy oligodeoxy-nucleotide that blocks NF-κB.

A method for modulating NF-κB dependent gene transcription in a cell comprised of modulating IKKα protein activity in the cell. The present invention also provides siRNA compositions and methods thereof for modulating NF-κB dependent gene transcription.

The present invention concerns double-stranded NF-κB decoy oligodeoxynucleotide (NF-κB dsODN) molecules that contain a core sequence capable of specific binding to an NF-κB transcription factor. In a particular aspect, the invention concerns NF-κB decoy molecules that preferentially bind p50 / p65 and / or cRel / p50 heterodimers over p50 / p50 homodimers. In another aspect, the invention concerns NF-κB decoy molecules with improved binding affinity to p65.

A class of novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) its stereoisomers thereof, or a solvate thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, where Z is CONR1R2 or CH2NR1R2 and where at least two of X1-X4 and / or X5-X8 is N or NR18, and R, Ra, Rb, Rc, Rd, R1, R2 and R18 are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

A class of novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I): where X is S, O or N; Z is —T—COOR1 or —T—COR1; and T, R, R1, Ra, Rb, Rc, Rd, Z, A and B are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

Methods and apparatus of providing a subject with post-operative, sustained-release of a biological agent within a synovial joint is disclosed. These methods involve securing a depot containing the biological agent to a ligament, tendon, muscle within the joint to provide sustained-release of the agent while allowing for normal joint articulation. This methodology may be utilized to provide for sustained-release of a biological agent useful in treating various traumas and disorders of the joint. Such biological agents include antagonists of inflammation-related proteins, such as TNF-α, IL-1β, IL-6, IL-8, NF-κB, High Mobility Group Box 1 (HMG-B1), IL-2, IL-15 and steroidal and non-steroidal anti-inflammatories. Other biological agents include anti-inflammatory cytokines such as IL-10, IL-4, IL-13, and TGF-β. The biological agents also include osteogenic and cartilage producing growth factors such as, but not limited to, BMP-2, BMP-4, BMP-6, BMP-7, BMP-8, and MIA CD-RAP. Finally, the biological agents include siRNA and / or therapeutic antibodies.

Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) or stereoisomers or prodrugs or solvates or pharmaceutically acceptable salts thereof, wherein A, B, J, K, Z, R, Ra, Rb, Rc, and Rd, are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

The invention features a method for the treatment or prevention of mucositis in an individual undergoing or preparing to undergo cancer treatment. The method includes administering a therapeutically effective amount of an inhibitor of NF-κB to an individual undergoing or preparing to undergo a treatment for cancer. In certain embodiments, the inhibitor is a compound having the formula: where R1 and R4 are OH, and R2 and R3 are independently OH or H, provided that when R1 and R2 are both OH, R1 and R2 cannot be disposed ortho to one another, and when R3 and R4 are both OH, R3 and R4 cannot be disposed ortho to one another. The compounds of formula I may be cis or trans.

The use of lipopeptides as inducers of NF-κB for the protection of mammals from the effects of apoptosis is described.

A method for modulating NF-κB dependent gene transcription in a cell comprised of modulating IKKα and IKKβ protein and protein activity in the cell. The present invention also provides siRNA compositions and methods thereof for modulating NF-κB dependent gene transcription.

A novel and effective strategy for organ transplantation is provided. A therapeutic agent and method for preventing an acute rejection in a transplanted organ and improving prognosis are provided. A therapeutic agent for suppressing a rejection in organ transplantation, which comprises an NF-κB decoy compound, is provided. Representatively, the organ transplantation is kidney transplantation. The therapeutic agent further comprises an ultrasonic inspection contrast agent. A therapeutic agent for improving prognosis in organ transplantation is also provided. The therapeutic agent is administered into a donor organ. The transfection efficiency of the NF-κB decoy compound into the organ may be enhanced by ultrasound treatment.

Inhibitors of bone calcium resorption are administered to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating non-calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-κB ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-κB gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene -19-nor-(20S)-1α,25-dihydroxyvitamin D3.

The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, inhibit the interaction of MUC1 with NF-κB or a STAT, and block inflammatory response mediated by NF-κB or STAT signaling.

Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I):an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which:Z is heterocyclo or heteroaryl;A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring;B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R5, R6, R7, and R8;J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted C1-3alkylene, C2-4alkenylene, and substituted C2-4alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring;R1 to R11 are as defined herein.Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

Methods and apparatus of providing a subject with post-operative, sustained-release of a biological agent within a synovial joint is disclosed. These methods involve securing a depot containing the biological agent to a ligament, tendon, muscle within the joint to provide sustained-release of the agent while allowing for normal joint articulation. This methodology may be utilized to provide for sustained-release of a biological agent useful in treating various traumas and disorders of the joint. Such biological agents include antagonists of inflammation-related proteins, such as TNF-α, IL-1β, IL-6, IL-8, NF-κB, High Mobility Group Box 1 (HMG-B1), IL-2, IL-15 and steroidal and non-steroidal anti-inflammatories. Other biological agents include anti-inflammatory cytokines such as IL-10, IL-4, IL-13, and TGF-β. The biological agents also include osteogenic and cartilage producing growth factors such as, but not limited to, BMP-2, BMP-4, BMP-6, BMP-7, BMP-8, and MIA CD-RAP. Finally, the biological agents include siRNA and / or therapeutic antibodies.