Abstract: Disclosed herein are bicyclic pyridines, such as thienopyridine, pyrrolopyridine, furopyridine compounds, and methods for treating cancers.

Abstract: Disclosed herein are bicyclic pyridines, such as thienopyridine, pyrrolopyridine, furopyridine compounds, and methods for treating cancers.

Abstract: The invention relates to the treatment of cancer. More particularly, the invention relates to the treatment of metastatic cancer. The invention provides new treatments for colon cancer patients who develop metastasis in the liver. The invention provides a method for treating hepatic metastatic colon cancer in a subject, the method comprising administering to the subject a small molecule selective inhibitor of CDK8/19 at a dosage that inhibits growth of the hepatic metastatic colon cancer, and does not cause a dose-limiting toxicity. The invention further provides a method for treating a subject having both a primary colon cancer tumor and hepatic metastatic colon cancer, the method comprising administering to the subject a small molecule selective inhibitor of CDK8/19 at a dosage that inhibits growth of the hepatic metastatic colon cancer, but does not significantly inhibit growth of the primary colon cancer tumor.

Abstract: The invention provides methods for suppressing neointimal formation resulting from vascular surgery, comprising administering to a patient having vascular surgery one or more inhibitors of CDK8/19.

Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.

Abstract: The invention provides a method for determining the activity of an inhibitor of a target protein that has a deleterious effect on cell growth. The principle of the claimed method is that a compound that inhibits the function of an overexpressed protein will relieve the detrimental effect of such overexpression in a concentration-dependent manner, thereby allowing the determination of the activity of the compound in inhibiting its target protein in live cells.

Abstract: The invention provides a method for treating a disease or disorder in a mammal which is caused by induced NFkB transcriptional activity in cells of the mammal, the method comprising administering to the mammal a compound that specifically inhibits one or more of CDK8 and CDK19.

Abstract: The invention provides a method for treating prostate cancer in a subject comprising administering to the subject an effective amount of a selective inhibitor of one or more of CDK8 and CDK19. In some embodiments the inhibitor inhibits CDK19. In some embodiments, the inhibitor inhibits CDK8 at a Kd of lower than 200 nM and/or inhibits CDK19 at a Kd of lower than 100 nM. In some embodiments, the prostate cancer is androgen independent. In some embodiments, the prostate cancer is androgen independent due to one or more of androgen receptor gene amplification, androgen receptor gene mutation, ligand-independent transactivation of androgen receptor and activation of intracellular androgen synthesis. In some embodiments, the inhibitor inhibits increased activity of NF-?B. In some embodiments, the inhibitor does not inhibit increased basal levels of NF-?B.

Abstract: Cancers that overexpress tyrosine kinase receptors of HER family are treated with drugs acting on these receptors. Although HER-targeting drugs have revolutionized the treatment of HER-positive cancers, high rates of primary and treatment-emergent resistance limit their clinical utility. The present inventors have now discovered that combining HER-targeting drugs with a selective inhibitor of CDK8/19 greatly improves the efficacy of such drugs, offering an improved approach to the treatment of HER-positive cancers.

Abstract: The invention provides a method for determining the efficacy of a small molecule for inhibiting cyclin-dependent kinase 8 (CDK8) and/or cyclin-dependent kinase 19 (CDK19), using STAT1 phosphorylation as a PD marker.

Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.

Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases.

Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.

Abstract: The invention provides a selective inhibitor of CDK8/19 for use in a method of treating a patient having estrogen receptor positive (ER+) breast cancer, including breast cancer that is resistant to antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8/19 is administered in combination with antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8/19 is administered to ER+HER2+ breast cancer patients in combination with HER2-targeting drugs.

Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases.

Abstract: The invention provides a method for treating a disease or disorder in a mammal which is caused by induced NFkB transcriptional activity in cells of the mammal, the method comprising administering to the mammal a compound that specifically inhibits one or more of CDK8 and CDK19.

Abstract: The invention provides a method for determining the activity of an inhibitor of a target protein that has a deleterious effect on cell growth. The principle of the claimed method is that a compound that inhibits the function of an overexpressed protein will relieve the detrimental effect of such overexpression in a concentration-dependent manner, thereby allowing the determination of the activity of the compound in inhibiting its target protein in live cells.

Abstract: The invention relates to compounds for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases.

Abstract: The invention relates to methods for high-throughput screening for compounds that modulate cell growth or promoter activity. The invention provides the use of cell lines with properly regulated promoter-reporter expression, suitable for high-throughput screening. More particularly, the invention relates to such screening to identify compounds that affect cell growth and/or that modulate the effect of cell cycle arrest on the function of a promoter that is responsive to cell cycle inhibition.

Abstract: The invention provides new gene targets for cancer chemotherapy, their use in assays for identifying new small molecule cancer chemotherapeutic agents, methods for inhibiting cancer cell growth comprising contacting a cell with a gene expression blocking agent that inhibits the expression of such genes and methods for therapeutic treatment of cancer in a mammal, comprising administering to the mammal such a gene expression blocking agent. A preferred gene target is coatomer protein zeta-1 subunit (COPZ1).