6307-89-7Relevant academic research and scientific papers
NOVOBIOCIN ANALOGUES AND TREATMENT OF POLYCYSTIC KIDNEY DISEASE
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, (2011/04/24)
Novobiocin analogues are useful in methods of treating, inhibiting, and/or preventing cyst formation in autosomal dominant polycystic kidney disease (ADPKD) in a subject. The disclosure provides methods of treating ADPKD comprising administering a therapeutically effective amount of a coumarin-3-carboxamide novobiocin analogue. Accordingly, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of mTOR pathway phosphoproteins P-mTOR, P-Akt and P-S6K, or combinations thereof. Further, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of Hsp-90 client proteins CFTR, ErbB2, c-Raf and Cdk4, or combinations thereof.
The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity
Donnelly, Alison C.,Mays, Jared R.,Burlison, Joseph A.,Nelson, John T.,Vielhauer, George,Holzbeierlein, Jeffrey,Blagg, Brian S. J.
experimental part, p. 8901 - 8920 (2009/04/11)
(Chemical Equation Presented) Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at ～700 μM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.
