387 results about "Cell Cycle Protein" patented technology

The invention provides a compound of the formula (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase: wherein A is a group R2 or CH2—R2 where R2 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; B is a bond or an acyclic linker group having a linking chain length of up to 3 atoms selected from C, N, S and O; R1 is hydrogen or a group selected from SO2Rb, SO2NR7R8, CONR7R8, NR7R9 and carbocyclic and heterocyclic groups having from 3 to 7 ring members; R3, R4, R5 and R6 are the same or different and are each selected from hydrogen, halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group Ra—Rb wherein Ra is a bond, O, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc or NRcSO2; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; Rc is hydrogen or C1-4 hydrocarbyl; X1 is O, S or NRc and X2 is ═O, ═S or ═NRc; R7 is selected from hydrogen and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; R8 is selected from R7 and carbocyclic and heterocyclic groups having from 3 to 12 ring members; R9 is selected from R8, COR8 and SO2R8; or NR7R8 or NR7R9 may each form a heterocyclic group having from 5 to 12 ring members; but excluding the compounds N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide and N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide.

In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

In its many embodiments, the present invention provides a novel class of imidazo[1,2-a]pyrazine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Biomarkers having expression patterns that correlate with a response of cells to treatment with one or more cdk modulating agents, and uses thereof. Also provided are methods for testing or predicting whether a mammal will respond therapeutically to a method of treating cancer that comprises administering an agent that modulates cdk activity.

Certain derivatives of acridones and benzothiadiazines have been found to have anti-cancer properties by virtue of their specific inhibition of the cyclin D dependent kinase CDK4. These molecules inhibit CDK4 activity more than they inhibit the activity of other such kinases (e.g. CDC2 and CDK2). This specificity results in an improved therapeutic index when used as drugs to treat susceptible cancers.

This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitors when administered to subjects.

The present disclosure identifies a novel subtype of follicular lymphoma (FL) characterized by dysregulation of the cyclin / CDK / RB proliferative pathway. This subtype of FL is associated with increased malignancy and mortality, relative to FL which is not associated with cell cycle dysregulation. Accordingly, this disclosure presents novel methods to subtype FL and stratify patient risk by detection of biomarkers associated with RB inactivation. This disclosure further presents novel therapies for the treatment of FL subtyped by inactivation of RB.

The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ic) wherein R1, R2, R3, R4, R5, R6, R7 and A have the meanings indicated in the claims. The invention also relates to processes for the preparation of the compounds of formula (Ia), to methods of inhibiting cyclin-dependent kinases and of inhibiting cell proliferation, to the use of the compounds of formula (Ic) in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of cyclin-dependent kinases such as cancer, to the use of the compounds of formula (Ic) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ic) either alone or in combination with another active agent, in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula (Ic) either alone or in combination with another active agent, together with pharmaceutically acceptable carrier substances and auxiliary substances.

The invention provides compounds of the formula (I):The compounds have activity against cyclin dependent kinases, glycogen synthase kinase and Auroa kinases and are therefore useful to treat cancer and viral diseases.

The present invention provides polypeptides, and polynucleotides encoding therefore, involved in the regulation of fibre initiation and / or elongation in fibre producing plants. In particular, the present invention provides methods of altering fibre initiation in cotton making use of transcription factors, regulatory proteins or cell cycle proteins produced at or around anthesis. The invention also relates to the use of these as markers of fibre production in plants including cotton.

The present invention relates to methods of suppressing neuronal death, such as is observed with ischemia-related diseases and disorders, including neuronal and cardiac conditions arizing from a sudden loss of oxygen and / or energy loss, and degenerative diseases, such as Alzheimer's disease to name just one. The methods involve the use of inhibitors that act primarily in a simultaneous manner on the cyclin-dependent kinases, CDK4 and CDK6.

This invention relates to compounds, compositions, and methods useful for modulating cyclin (e.g., cyclin D1) and / or cyclin dependent kinase (CDK) 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 cyclin (e.g., cyclin D1) and / or cyclin dependent kinase (CDK) 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 cyclin (e.g., cyclin D1) and / or cyclin dependent kinase (CDK) genes.

The present invention relates to inhibitors of general Formula (I) of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to compounds for preventing and / or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases.

In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or compositions.

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

A process is provided for modifying growth or architecture of plants by altering the level or the functional level of a cell division controlling protein, preferably a cell-division controlling protein that binds phosphorylates retinoblasoma-link proteins, more preferably a cyclin, particularly a D-type cyclin within cells of a plant. Also provided are chimeric genes comprising a transcribed DNA region encoding an RNA or a protein, which when expressed either increases or decreases the level or functional level of a cell-division controlling protein, and plant cells and plants expressing such chimeric genes.

The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ia),wherein R1, R2, R3, R4, R5, R6, R7 and A have the meanings indicated in the claims. The invention also relates to processes for the preparation of the compounds of formula (Ia), to methods of inhibiting cyclin-dependent kinases and of inhibiting cell proliferation, to the use of the compounds of formula (Ia) in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of cyclin-dependent kinases such as cancer, to the use of the compounds of formula (Ia) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ia) either alone or in combination with another active agent, in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula (Ia) either alone or in combination with another active agent, together with pharmaceutically acceptable carrier substances and auxiliary substances.

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

In its many embodiments, the present invention provides a novel class of imidazo[1,2-a]pyrazine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

The present invention is directed to a process for inhibiting the replication of human immunodeficiency virus-1 (HIV-1), by contacting a cell with at least one compound according to Formula I.The substituent groups R1, R2, R3, X, Y, Z, A and B are as defined above. Also contemplated is a method for treating or preventing a HIV-1 infection in a subject, by administering a therapeutically effective amount of at least one compound according to Formula I, as well as a method for modulating the activity of a cyclin dependent kinase (cdk) in a cell infected with HIV-1 using a Formula I compound.

Disclosed are polymorphs of the isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.