Abstract: Disclosed herein are CDK8/19 degraders and methods of making and using the same. The CDK8/19 degrader is a heterobifunctional compound, or a pharmaceutically acceptable salt thereof, comprising a CDK8/19 targeting moiety, a ubiquitin ligase ligand moiety, and a linker linking the CDK8/19 targeting moiety and the ubiquitin ligase ligand moiety.

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted quinoline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

Abstract: Disclosed is a carbon fiber preform, a preparation method therefor and a preparation method for carbon/carbon composites, falling within the technical field of composites. The carbon fiber preform provided by the present disclosure includes a plurality of stacked carbon fiber cloths and prestressed layers arranged between every two of adjacent carbon fiber cloths, the prestressed layer including a boron-containing phenol-formaldehyde resin coating and carbon fiber bundles distributed within the boron-containing phenol-formaldehyde resin coating. In the present disclosure, the prestressed layers are formed by adding the carbon fiber bundles and a boron-containing phenol-formaldehyde resin precursor to a two dimensional (2D) stacked preform, thereby counteracting internal stresses during carbonization and obtaining a carbon/carbon composite having higher strength and being less prone to cracking.

Abstract: A graphitization furnace includes a furnace body, an upper lining, an insulating lining, a lower lining, a positive electrode and a negative electrode. The upper lining, the insulating lining and the lower lining are all disposed as attached to an inner wall of the furnace body, and the upper lining, the insulating lining and the lower lining sequentially abut against one another along a direction from top to bottom, and the upper lining, the insulating lining and the lower lining are all substantially provided with first through holes with a common axis. The positive electrode is substantially disposed vertically, a lower end of the positive electrode is disposed within the upper lining, the negative electrode is substantially disposed horizontally, and a middle part of the negative electrode is provided with a second through hole for passing raw ingredients.

Abstract: Disclosed herein are methods for treating a subject comprising the administration of an effective amount of an inhibitor of CDK8 and CDK19 to a subject in need of a treatment for a cytokine storm or elevated amounts of a multiplicity of different cytokine-storm mediating cytokines.

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

Abstract: Disclosed herein are methods of using 3-amino-4-(4-(4 (dimethylcarbamoyl) phenyl)-1,4-diazepan-1-yl)thieno[2,3-b]pyridine-2-carboxamide or deuterated analogues thereof for treating cancers and pharmaceutical compositions comprising the same.

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

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted quinoline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

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. In some embodiments, inhibition of one or more genes by AR is not inhibited.

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. In some embodiments, inhibition of one or more genes by AR is not inhibited.