16704-79-3Relevant articles and documents
Proteome interrogation using nanoprobes to identify targets of a cancer-killing molecule
Li, Liwen,Zhang, Qiu,Liu, Aifeng,Li, Xiue,Zhou, Hongyu,Liu, Yin,Yan, Bing
supporting information; experimental part, p. 6886 - 6889 (2011/06/21)
We report a generic approach for identification of target proteins of therapeutic molecules using nanoprobes. Nanoprobes verify the integrity of nanoparticle- bound ligands in live cells and pull down target proteins from the cellular proteome, providing very important information on drug targets and mechanisms of action. As an example, target proteins as R-tubulin and HSP 90 have been identified and validated.
4-Pyridylanilinothiazoles that selectively target von Hippel - Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
Hay, Michael P.,Turcotte, Sandra,Flanagan, Jack U.,Bonnet, Muriel,Chan, Denise A.,Sutphin, Patrick D.,Nguyen, Phuong,Giaccia, Amato J.,Denny, William A.
supporting information; experimental part, p. 787 - 797 (2010/07/05)
Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel-Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure-activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different chemical features to potency illustrates a region, adjacent to the pyridyl ring, with potential for further development. Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC. 2009 American Chemical Society.
HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT
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Page/Page column 102-103, (2009/10/22)
Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.
COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRUSES AND CANCER
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Page/Page column 25; 26, (2010/11/26)
The present invention relates to compounds according to the formula I: Where Ra is H or an optionally OH-substituted C1-C3 alkyl; R1 is OR1, an optionally substituted C4-12 carbocyclic group which may be saturated or unsaturated (including aromatic) or an optionally substituted heterocyclic group; R1 is an optionally substituted C1-C14 hydrocarbyl group or an optionally substituted heterocyclic group;; R2 , R3 and R4 are each independently H, an optionally substituted C1-C4 alkyl group (preferably CH3, CH2CH3 or CF3), halogen (preferably F, Cl, Br), OR, CN, NO2, a C1-C6 thioether, a C1-C6 thioester group, an optionally substituted CO2R group, an optionally substituted COR group or an optionally substituted OCOR group (preferably R4 is H); R is H or an optionally substituted C1-C6 alkyl group; RHET is an optionally substituted heterocyclic group; and pharmaceutically acceptable salts, solvates or polymorphs thereof.
