摘要:
Aromatic compounds for treating various diseases and pathologies are disclosed. The methods use of such compounds are also provided. Accordingly, the present invention makes available methods and compositions for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function.
摘要:
The methods of the invention allow extremely high throughput screening of chemicals against a large number of pharmacologically relevant targets. All of the pharmacologically relevant targets are expressed in cells, which are then screened against a fluorescently-tagged combinatorial library. Binding of the small molecules to the cells is then detected by fluorescence activated cell sorting or imaging.
摘要:
The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity. Such methods and reagents may also inhibit the hedgehog pathway in normal cells, e.g., where normal levels of hedgehog signalling are unwanted.
摘要:
Aromatic compounds for treating various diseases and pathologies are disclosed. The methods use of such compounds are also provided. Accordingly, the present invention makes available methods and compositions for inhibiting aberrant growth states in cells having Wnt receptors.
摘要:
Methods are provided in which a sterol-depleting agent such as β-cyclodextrin (βCD), is used to modulate signaling by a differentiation signaling protein such as Hedgehog protein or a BMP in vitro. As illustrated herein, the use of βCD in conjunction with Sonic Hedgehog N-terminal peptide (ShhN) causes substantially all of the cells in neural plate explants to differentiate as neurons, such as motor neurons. Also provided are cell therapy methods and screening methods that rely on the modulation of signaling of a differentiation signaling protein such as Hedgehog, by a sterol-depleting agent such as βCD.
摘要:
Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in prostate tumors, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating a prostate cancer associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of identifying a prostate tumor of a subject as, or as capable of becoming lethal and/or metastatic.
摘要:
The present invention makes available, inter alia, methods and reagents for modulating smoothened-dependent pathway activation. In certain embodiments, the subject methods can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function mutations.
摘要:
The present invention provides transcription factors associated with the hedgehog signaling pathway that are regulated by dephosphorylation by phosphatases. Hedgehog response elements (HRE) that interact with the dephosphorylated transcription factors are also provided as well as methods for identifying compounds that are phosphatase inhibitors. Methods of treating tumors in a subject by modulating the phosphorylation of the transcription factor are also included.
摘要:
The present invention makes available assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.
摘要:
The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.