Abstract: Various compounds and pharmaceutically acceptable salts thereof are provided capable of binding cyclin-dependent kinase inhibitor 1B. The compounds can have a structure according to Formula I or Formula II as detailed herein. The compounds can include SJ747, SJ749, SJ755, SJ757. Pharmaceutical formulations containing the compounds or pharmaceutically acceptable salts are also provided along with methods of use thereof. The formulations and methods can be useful for treating cancer. In some aspects, the cancer is associated with a mislocalization of the intrinsically disordered protein p27. In some aspects, the cancer is resistant to an anticancer therapy. The pharmaceutical formulation can therefore include a second active agent and/or can be given in combination with a second active agent such as a cancer therapeutic. In various aspects, methods of promoting reentry into the cell division cycle in a subject in need thereof using compounds and formulations described herein are also provided.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R21 or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope.

Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R21 or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope.

Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R2i or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope.

Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R2i or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope.

Abstract: The present invention discloses that the binding of Arf with Dm2, important components of the p53 tumor suppressor pathway, results in specific domains of both proteins undergoing a dramatic transition from dynamically disordered conformations to amyloid-like structures comprised of anti-parallel ?-strands. The invention exploits this discovery by providing unique methods for identifying and/or designing compounds that mimic, inhibit and/or enhance the effect of Arf on Dm2. The present invention also provides specific peptides derived from the binding domains of Arf and Dm2 which co-assemble into supramolecular structures comprised of binary anti-parallel ?-strands. The disclosed peptides may represent structural prototypes for a broader class of peptides that is capable of assembly into supramolecular structures.

Abstract: The present invention discloses that the binding of Arf with Dm2, important components of the p53 tumor suppressor pathway, results in specific domains of both proteins undergoing a dramatic transition from dynamically disordered conformations to amyloid-like structures comprised of anti-parallel &bgr;-strands. The invention exploits this discovery by providing unique methods for identifying and/or designing compounds that mimic, inhibit and/or enhance the effect of Arf on Dm2. The present invention also provides specific peptides derived from the binding domains of Arf and Dm2 which co-assemble into supramolecular structures comprised of binary anti-parallel &bgr;-strands. The disclosed peptides may represent structural prototypes for a broader class of peptides that is capable of assembly into supramolecular structures.

Abstract: The present invention discloses that the binding of Arf with Dm2 results in specific domains of both proteins undergoing a dramatic transition from disordered conformations to extended structures comprised of &bgr;-strands. The presence of these specific domains is necessary and sufficient for the formation of the highly stable extended &bgr; structures formed between these two proteins. The present invention further exploits this discovery by providing unique methods for identifying and/or designing compounds that mimic, inhibit and/or enhance the effect of Arf on Dm2. The present invention also provides specific protein fragments derived from Arf and Dm2 that play a critical role in the binding of these two important regulatory proteins.