84 results about "Cell Cycle Protein" patented technology

The present application provides compounds of Formula (I):or a pharmaceutically acceptable salt thereof, that are inhibitors of cyclin-dependent kinase 4 (CDK4), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

The present invention relates to an aryl substituent-containing degradation agent for cyclin-dependent kinase 12 / 13 (CDK12 / 13), a preparation method therefor, and a pharmaceutical composition and use thereof. The degradation agent for CDK12 / 13 of the present invention has a structure represented by formula (I). The compound can be used as a protein kinase degradation agent, and can effectively and highly selectively degrade a CDK12 / 13 protein and inhibit proliferation, migration, and invasion of various tumor cells.

The present disclosure provides certain bifunctional compounds that cause degradation of Cyclin-dependent kinase 2 (CDK2) via ubiquitin proteasome pathway and are therefore useful for the treatment of diseases mediated by CDK2. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

This invention relates to combination therapies comprising an inhibitor of anaplastic lymphoma kinase (ALK) and, an inhibitor of cyclin dependent kinase 4 and 6 (CDK4 / 6 inhibitor) or an inhibitor of cyclin dependent kinase 2, 4 and 6 (CDK2 / 4 / 6 inhibitor), and associated methods of treatment, combinations, pharmaceutical compositions and uses thereof.

Disclosed herein are methods for increasing sensitivity of a cancer cell to alternating electric fields by administering an AKT inhibitor, a mammalian target of rapamycin (mTOR) inhibitor, a Phosphatidylinositol 3-Kinase (PI3K) inhibitor, and / or a Glycogen synthase kinase 3β (GSK3β) inhibitor. Disclosed are methods of increasing treatment efficacy comprising applying alternating electric fields to a target site of the subject for a period of time, the alternating electric fields having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an mTOR inhibitor, AKT inhibitor, PI3K inhibitor, or GSK3β inhibitor to the subject. Disclosed are methods of reducing viability of cancer cells using alternating electric fields for a period of time, the alternating electric fields having a frequency and field strength in combination with either an mTOR inhibitor, AKT inhibitor, PI3K inhibitor, or GSK3β inhibitor and / or a composition or compound that increases cyclin D1. Disclosed are methods of increasing apoptosis of a cancer cell comprising exposing the cancer cell to alternating electric fields for a period of time, the alternating electric fields having a frequency and field strength; and exposing the cancer cell to a PI3K inhibitor.

The invention relates to compounds which inhibit Cyclin-Dependent Kinases such as CDK2 (Cyclin-Dependent Kinase 2 or Cell Division protein Kinase 2) and CDK4 (Cyclin-Dependent Kinase 4 or Cell Division protein Kinase 4), and to processes for the preparation of said compounds, pharmaceutical compositions comprising said compounds, and use of said compounds in the treatment of conditions, diseases and disorders mediated by CDK2 and / or CDK4.

The present invention relates to pharmaceutical compounds of formula (I) and pharmaceutical compositions containing said compounds, processes for the preparation of said compounds, and the use of said compounds as inhibitors of cyclin-dependent kinase 7 (CDK7), and their use in the treatment of diseases, such as cancer. [Formula 1] TIFF2023554673000617.tif33128

The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases in a subject, wherein the proliferative diseases include cancer, benign neoplasm, angiogenesis, inflammatory disease, autoinflammatory disease, and autoimmune disease, and the cancer includes leukemia, melanoma, multiple myeloma. Treatment of a subject having a proliferative disease with the compounds or compositions of the present invention can inhibit abnormal activity of cyclin-dependent kinase 7, thus inducing apoptosis and / or inhibiting transcription in the subject.

The present invention relates to pharmaceutical compounds of Formula (I) and pharmaceutical compositions comprising said compounds, methods for preparing said compounds and the use of said compounds as Cyclin-Dependent Kinase 7 (CDK7) inhibitors and their use in the treatment of diseases, such as cancer.

The application discloses a bifunctional compound and use thereof, the bifunctional compound is a bifunctional compound with K-L-S structure, wherein: K is a targeting group of cyclin 7CDK7;S is a covalent group targeting cysteine or lysine on CDK7 protein;L is a divalent linking group chemically connecting the targeting group K and the covalent group S;The bifunctional compound or does not contain divalent linking group L, and the targeting group K is directly connected with the covalent group S.The bifunctional compound or its pharmaceutically acceptable salt, ester, hydrate, solvate or stereoisomer and the pharmaceutical composition containing the same show pharmacological activity related to degradation, inhibition of target protein CDK7, and can be used for preventing and treating CDK7 related diseases or disorders.

Disclosed herein are methods and agents for the treatment and / or prevention of cyclin-dependent kinase-like 5 (CDKL5) deficiency. In particular, disclosed herein are compounds or compositions for increasing cyclin-dependent kinase-like 2 (CDKL2) in a subject, for example, in the brain of a subject, and the use of such compounds and compositions in methods for treating CDKL5 deficiency.

The present invention relates to a compound of formula (I), a compound-linker construct comprising the compound, and a conjugate comprising the compound-linker and a targeting moiety. The compound of the present invention has the ability to stimulate and / or induce, particularly induce degradation of a target protein. Such a target protein may be a protein involved in diseases, like cancer, metabolic disorder, infectious disease and / or neurological disorder, namely in particular cyclin K (CCNK) and / or CDK12 and / or CDK13. The present invention also relates to the compound, the compound-linker construct and the conjugate for use as medicament, preferably for use in treating specific diseases as disclosed herein.

This invention discloses *Bifidobacterium longum* with anti-aging functions and its applications, belonging to the field of microbial technology. The *Bifidobacterium longum* BBS 02 provided by this invention can promote cell vitality and proliferation, inhibit the high activity of β-galactosidase in senescent cells, and inhibit the high expression of the cyclin-dependent kinase inhibitor gene Cdkn1a, thereby achieving an anti-aging effect. The *Bifidobacterium longum* BBS 02 can be used to prepare edible nutrients or skin nutrients.

The present disclosure relates to a method of determining a prognostic outlook for patients having metastatic breast cancer. The method includes receiving imaging data from an image of a patient that is receiving or that is to receive cycline dependent kinase 4 and 6 (CDK 4 / 6) inhibitor therapy for hormone receptor-positive (HR+) metastatic breast cancer. Radiomic heterogeneity features are extracted from imaging data associated with a metastasis within the imaging. A prognostic marker is determined from the radiomic heterogeneity features. The prognostic marker is indicative of a response of the patient to CDK 4 / 6 inhibitor therapy for HR+ metastatic breast cancer.

The present invention relates to pharmaceutical compounds of Formula (I) and pharmaceutical compositions comprising said compounds, to methods for preparing said compounds and to the use of said compounds as inhibitors of cyclin-dependent kinase 7 (CDK7) and their use in the treatment of diseases, such as cancer.

The present application provides compounds of Formula (I):or a pharmaceutically acceptable salt thereof, that are inhibitors of cyclin-dependent kinase 4 (CDK4), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

The disclosure relates to adeno-associated (AAV) particles comprising viral genomes encoding cyclin-dependent kinase-like 5 (CDKL5) proteins and peptides, compositions comprising said AAV particles, and methods for making and delivering said AAV particles to a cell or subject. The AAV particles, compositions, and methods of the present disclosure are useful for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a CDKL5 deficiency disorder (CDD), developmental and epileptic encephalopathy 2, atypical Rett syndrome, and / or other CDKL5-related disorders or at least one symptom thereof.

Provided herein are bifunctional compounds that bind cyclin-dependent kinase 9 (CDK9) and / or promote targeted ubiquitination for the degradation of CDK9, a protein whose dysregulation is implicated in certain cancers. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer, methods of promoting the degradation of CDK9 and / or IKZF1, and methods of promoting the selective degradation of CDK9 (e.g., over IKZF1) by a compound or composition described herein.

This specification discloses methods for identifying stable control loci for use in fluorescence in situ hybridization (FISH) assays, and methods for determining whether copy number changes (e.g., amplification) of a target genomic locus (e.g., a gene, e.g., cyclin E1 (CCNE1)) have occurred in a biological sample (e.g., a non-neoplastic sample, a pre-neoplastic lesion, and / or a tumor). In particular, this disclosure provides an expanded repertoire of genomic loci that can serve as stable controls (e.g., stable control loci) for FISH assays aimed at determining copy number changes of a target genomic locus.

This disclosure provides certain bifunctional compounds that induce the degradation of cyclin-dependent kinase 2 (CDK2) via the ubiquitin-proteasome pathway, and are therefore intended for the treatment of CDK2-mediated diseases. Pharmaceutical compositions containing such compounds and methods for preparing such compounds are also provided.

Disclosed herein are methods for identifying stable control loci for fluorescence in situ hybridization (FISH) assays and for determining whether a copy number change (e.g., amplification) of a target genomic locus (e.g., a gene, e.g., cyclin E1 (CCNE1)) has occurred in a biological sample (e.g., a non-tumor sample, a precancerous lesion, and / or a tumor). In particular, the present disclosure provides an extended repository of genomic loci that can act as a stable control (e.g., a stable control locus) for a FISH assay intended to determine copy number changes in the target genomic locus.

Disclosed are compounds of Formula (I): or stereoisomers, tautomers, or salts thereof, wherein X, Y, W, Z, L, R3, R4, R5, R6, R7, m, n, and p are defined herein. Also disclosed are methods of using such compounds to decrease the level Cyclin E1; and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of proliferative disorders, such as cancer.

The invention relates to pharmaceutical compounds of formula (I) and pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds as inhibitors of cyclin-dependent kinase 7 (CDK7) and to their use in the treatment of diseases, e.g., cancer.

Compound of formula (I), JPEG2026521124000638.jpg54170 The intermediate and a method for manufacturing the same are disclosed herein. Furthermore, this specification also describes the use of such compounds and compositions for the treatment of diseases and disorders mediated by at least one or more cyclins, including cancer.

The present invention relates to an improved method for diagnosing homologous recombination deficiencies (HRDs) in tumors. The method according to the present invention comprises the steps of: evaluating the number of large genomic alterations (LGAs) in a tumor sample by obtaining a copy number alteration (CNA) profile by shallow coverage whole-genome sequencing (sWGS); and determining an LGA score corresponding to the number of LGAs adjusted for the complexity of the tumor genome and the presence of one or two markers selected from a group of markers consisting of (1) phenotypes associated with mutations in cyclin-dependent kinase 12 (CDK12) with multiple intermediate gains in the CNA profile; (2) amplification of cyclin E1 (CCNE1); (3) amplification of human epidermal growth factor receptor-2 (HER2); and (4) phenotypes of amplification at multiple sites.

The present disclosure provides methods of using combination therapies to treat cancer. These methods are based on inhibiting cyclin proteins along with proteins along the Cyclin Axis. Thus, a method of the disclosure may generally be practiced by administering to an individual having cancer a cytocidal inhibitor of cyclin, along with a therapeutic agent that targets other molecules involved in pathways that promote cyclin activity. These therapeutic agents may target biomarkers on the surface of a cancer cell and that promote cyclin activity as well as intracellular proteins involved in pathways that affect, or are affected by, cyclin activity.

The present application provides imidazolyl pyrimidinylamine inhibitors of cyclin-dependent kinase 2 (CDK2), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.