49 results about "Pathway signaling" patented technology

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Indazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole-3-carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

The present invention relates to methods for treating cancer comprising utilizing a combination of signal transduction inhibitors. More specifically, the present invention relates to combinations of so called cell cycle inhibitors with mitogen stimulated kinase signal transduction inhibitors, more specifically combinations of CDK inhibitors with mitogen stimulated kinase signal transduction inhibitors, more preferably MEK inhibitors. Other embodiments of the invention relate to additional combinations of the aforesaid combinations with standard anti-cancer agents such as cytotoxic agents, palliatives and antiangiogenics. Most specifically this invention relates to combinations of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one including salt forms, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor, in combination with one or more MEK inhibitors, most preferably N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide. The aforementioned combinations are useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.

Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.

The present invention relates to the use of specific EGF-receptor antagonists for preparing a pharmaceutical composition for the prevention and/or treatment of benign prostatic hyperplasia and/or prostatic hypertrophy, a method for the treatment or prevention of benign prostatic hyperplasia/prostatic hypertrophy comprising administering an EGF-receptor antagonist of groups (A), (B) or (C), described herein optionally in combination with known compounds for the treatment of benign prostatic hyperplasia/prostatic hypertrophy, as well as associated pharmaceutical compositions.

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

The invention relates to the use of: (a) an isolated gene sequence that is down-regulated in the spinal cord in response to streptozocin-induced diabetes; (b) an isolated gene sequence comprising a nucleic acid sequence of Tables I to X. (c) an isolated gene sequence having at least 80% sequence identity with a nucleic acid sequence of Tables I to X; (d) an isolated nucleic acid sequence that is hybridizable to any of the gene sequences according to (a), (b) or (c) under stringent hybridisation conditions; (e) a recombinant vector comprising a gene sequence or nucleic acid sequence according to any one of (a) to (d); (f) a host cell containing the vector according to (e); (g) a non-human animal having in its genome an introduced gene sequence or nucleic acid sequence or a removed or down-regulated gene sequence or nucleic acid sequence according to any one of (a) to (d); (h) an isolated polypeptide comprising an amino acid sequence at least 90% identical to an amino acid sequence encoded by a nucleotide sequence according to any one of (a) to (d), or a polypeptide variant thereof with sequential amino acid deletions from the C terminus and/or the N-terminus; or (i) an isolated polypeptide encoded by a nucleotide sequence according to any one of (a) to (d); or (k) an isolated antibody that binds specifically to a polypeptide according to (h) or (i); in the screening of compounds for the treatment of pain, or for the diagnosis of pain. The invention also relates to the use of naturally occurring compounds such as peptide ligands of the expression products of the above gene sequences and their associated signal transduction pathways for use in the treatment of pain.

The invention relates to the use of: (a) an isolated gene sequence that is down-regulated in the spinal cord of a mammal in response to mechanistically distinct first and second models of neuropathic or central sensitization pain; (b) an isolated gene sequence comprising a nucleic acid sequence of any of Tables I to VI; (c) an isolated gene sequence having at least 80% sequence identity with a nucleic acid sequence of any of Tables I to VI; (d) an isolated nucleic acid sequence that is hybridizable to any of the gene sequences according to (a), (b) or (c) under stringent hybridisation conditions; (e) a recombinant vector comprising a gene sequence or nucleic acid sequence according to any one of (a) to (d); (f) a host cell containing the vector according to (e); (g) a non-human animal having in its genome an introduced gene sequence or nucleic acid sequence or a removed or down-regulated gene sequence or nucleic acid sequence according to any one of (a) to (d); (h) an isolated polypeptide comprising an amino acid sequence at least 90% identical to an amino acid sequence encoded by a nucleotide sequence according to any one of (a) to (d), or a variant polypeptide thereof with sequential amino acid deletions from the C terminus and/or the N-terminus; (i) an isolated polypeptide encoded by a nucleotide sequence according to any one of (a) to (d); or (j) an isolated antibody that binds specifically to a polypeptide according to (h) or (i); in the screening of compounds for the treatment of pain, or for the diagnosis of pain. The invention also relates to the use of naturally occurring compounds such as peptide ligands of the expression products of the above gene sequences and their associated signal transduction pathways for use in the treatment of pain.

The invention relates to the use of: (a) an isolated gene sequence that is up regulated in the spinal cord in response to streptozocin-induced diabetes; (b) an isolated gene sequence comprising a nucleic acid sequence of Tables I to X. (c) an isolated gene sequence having at least 80% sequence identity with a nucleic acid sequence of Tables I to X; (d) an isolated nucleic acid sequence that is hybridizable to any of the gene sequences according to (a), (b) or (c) under stringent hybridisation conditions; (e) a recombinant vector comprising a gene sequence or nucleic acid sequence according to any one of (a) to (d); (f) a host cell containing the vector according to (e); (g) a non-human animal having in its genome an introduced gene sequence or nucleic acid sequence or a removed or down-regulated gene sequence or nucleic acid sequence according to any one of (a) to (d); (h) an isolated polypeptide comprising an amino acid sequence at least 90% identical to an amino acid sequence encoded by a nucleotide sequence according to any one of (a) to (d), or a polypeptide variant thereof with sequential amino acid deletions from the C terminus and/or the N-terminus; or (i) an isolated polypeptide encoded by a nucleotide sequence according to any one of (a) to (d); or (k) an isolated antibody that binds specifically to a polypeptide according to (h) or (i); in the screening of compounds for the treatment of pain, or for the diagnosis of pain. The invention also relates to the use of naturally occurring compounds such as peptide ligands of the expression products of the above gene sequences and their associated signal transduction pathways for use in the treatment of pain.

The present invention relates to a set of biomarkers, microarrays that provide for detection thereof, an expression signature comprising 16 genes or a subset thereof, and the use thereof in determining the regulation status of IL-6/STAT3 signaling pathway in a cell sample or subject, as well as compositions for the detection thereof. The regulation status of IL-6/STAT3 signaling pathway in a cell sample or subject may be assayed based on the level of expression of one or more of these genes. The methods and compositions provided herein may be used to evaluate IL-6/STAT3 pathway regulation status in a sample; classify a cell sample as having a deregulated or regulated IL-6/STAT3 signaling pathway; determine whether an agent modulates the IL-6/STAT3 signaling pathway; predict the response of a subject to an agent that modulates the IL-6/STAT3 signaling pathway; assign treatment to a subject; and/or evaluate the pharmacodynamic effects of therapies designed to regulate IL-6/STAT3 pathway signaling. Expression of the biomarkers is preferably determined by RT-PCR using SYBR Green methods, and the expression data analyzed and compared to a control sample by use of the random forest method.

The invention is directed at a method for predicting a patient's responsiveness to a CHK1 inhibitor The method includes providing a sample from a test patient who is being treated with a DNA damaging agent; and determining for the presence of an activated CHK1 signal transduction pathway molecule, wherein the presence of an activated CHK1 signal transduction pathway molecule is indicative that a CHK1 inhibitor should be administered to the patient.

The present invention provides methods comprising combination therapy for treating cancer. In particular, the present invention provides Wnt pathway inhibitors in combination with MAPK pathway inhibitors for the treatment of cancer and other diseases. In some embodiments, the MAPK pathway signaling activation is due to a mutation in a MAPK pathway component. In some embodiments, the MAPK pathway signaling component is Ras, Raf, MEK, or ERK.

The present invention relates to a method for increasing retrovirus transcription in an infected eukaryotic cell, comprising increasing Wnt pathway signaling in said cell such that transcription of said retrovirus is increased. Also, the present invention relates to a method of treating a subject infected with a retrovirus, said method comprising administering to said subject an activator of the Wnt pathway in an amount that increased Wnt pathway signaling in resting memory CD4+ T cells of said subject such that the retroviral long terminal repeat (LTR) in said cells is activated or de-repressed.

The invention provides an androstane derivative, a preparation method and applications thereof, and belongs to the technical field of medicine. According to the present invention, the androstane derivative has good inhibitory effect on Hedgehog signaling pathway so as to provide an effective treatment drug for patients with chronic myelogenous leukemia; the results of the embodiments show that the androstane derivative has the Hedgehog pathway signaling inhibition average IC50 value measured by using mouse [s12] and human [MZ24] Gli reporter cell lines of 0.020 [mu]m while the average IC50 value of the existing FDA-approved Hedgehog pathway inhibitor is 0.022 [mu]M, such that the androstane derivative has Hedgehog signaling pathway inhibition effect, and further achieve the effect comparable to Vismodegib.

Indazole compounds that modulate and/or inhibit the ophthalmic diseases and the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating ophthalmic diseases and cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

The present invention describes methods of inhibiting the pro-inflammatory response of human peripheral blood mononuclear cells or polymorphonuclear cells, or fixed tissue cells. The cells are contacted with a pro-inflammatory agent to stimulate a pro-inflammatory response. The cells are then contacted with G protein kinase signaling pathway modifiers, thereby inhibiting G protein mediated inflammatory response signaling pathways. The present invention describes receptor complexes wherein G protein kinase signaling pathway modifiers bind to cell surface receptors on human peripheral blood mononuclear cells or polymorphonuclear cells stimulated with proinflammatory agents.