Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Provided is a method for improving treatment of a neoplastic condition by combining a therapeutically effective amount of a polyADP-ribose polymerase inhibitor with a therapeutically effective amount of a compound which triggers the release of nucleolin from the G-quadruplexes in rDNA. As specifically exemplified, the compound which increases nucleolin binding is a substituted quinobenzoxazine analog, for example CX-3543.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Provided is a method for improving treatment of a neoplastic condition by combining a therapeutically effective amount of a polyADP-ribose polymerase inhibitor with a therapeutically effective amount of a compound which triggers the release of nucleolin from the G-quadruplexes in rDNA. As specifically exemplified, the compound which increases nucleolin binding is a substituted quinobenzoxazine analog, for example CX-3543.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that the nucleotide sequences (GGA)4 (SEQ ID NO: 1) and (GGA)3GG (SEQ ID NO: 2) form biologically significant quadruplex structures. Thus, provided herein are methods for identifying molecules that modulate the biological activity of quadruplex DNA comprising the nucleotide sequence (GGA)4 (SEQ ID NO: 1) or the nucleotide sequence (GGA)3GG (SEQ ID NO: 2), and specifically, methods for identifying molecules that bind such quadruplexes. Also provided herein are methods for modulating the biological activity of a biologically significant native quadruplex DNA with a molecule identified by the methods described herein.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from: and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Abstract: Expanded porphyrin comprising substitutions for at least two NH groups by S, Se or Te are non-photoactive and are selective for binding G-quadruplexes characteristic of the c-MYC control region. Accordingly, these expanded porphyrins are useful to modulate the expression of genes controlled by the formation of c-MYC type G-quadruplexes, such as c-MYC itself.

Abstract: Certain non-nucleoside compounds that will selectively inhibit telomerase by targeting the nucleic add structures, such as G-quadruplexes, that may be associated with human telomeres or telomerase have been identified. Inhibition of human telomerase by two perylenetetracarboxylic acid diimides and a carbocyanine has been demonstrated. 1H-NMR studies have evidenced the stabilization of a G-quadruplex by the perylenetetracarboxylic acid diimide compounds and provided evidence that these and structurally related compounds inhibit the telomerase enzyme by a mechanism consistent with interaction with G-quadruplex structures.

Abstract: Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that the nucleotide sequences (GGA)4 and (GGA)3GG form biologically significant quadruplex structures. Thus, provided herein are methods for identifying molecules that modulate the biological activity of quadruplex DNA comprising the nucleotide sequence (GGA)4 or the nucleotide sequence (GGA)3GG, and specifically, methods for identifying molecules that bind such quadruplexes. Also provided herein are methods for modulating the biological activity of a biologically significant native quadruplex DNA with a molecule identified by the methods described herein.

Abstract: Expanded porphyrin comprising substitutions for at least two NH groups by S, Se or Te are non-photoactive and are selective for binding G-quadruplexes characteristic of the c-MYC control region. Accordingly, these expanded porphyrins are useful to modulate the expression of genes controlled by the formation of c-MYC type G-quadruplexes, such as c-MYC itself.

Abstract: The present invention relates to methods for stimulating osteoblast proliferation and methods for selecting pharmacologically active compounds useful for stimulating osteoblast proliferation.

Abstract: Certain non-nucleoside compounds that will selectively inhibit telomerase by targeting the nucleic add structures, such as G-quadruplexes, that may be associated with human telomeres or telomerase have been identified. Inhibition of human telomerase by two perylenetetracarboxylic acid diimides and a carbocyanine has been demonstrated. 1H-NMR studies have evidenced the stabilization of a G-quadruplex by the perylenetetracarboxylic acid diimide compounds and provided evidence that these and structurally related compounds inhibit the telomerase enzyme by a mechanism consistent with interaction with G-quadruplex structures.

Abstract: Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that a chair conformation is biologically significant. Also, it has been determined that certain mutations in quadruplex forming nucleotide sequences destabilize quadruplex structure and are associated with cancer. Thus, provided herein are quadruplex-destabilized nucleic acid acids, cancer diagnostics and prognostics, methods for using the cancer diagnostics and prognostics to prevent and/or treat cancer, nucleic acid therapeutics that target quadruplex-destabilized nucleotide sequences and methods, methods for identifying compounds that modulate the biological activity of a native quadruplex DNA in a chair conformation, and methods for modulating the biological activity of a native quadruplex DNA with a compound identified by the methods described herein.