58933-52-1Relevant articles and documents
A Red-Light-Activated Ruthenium-Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells
Lameijer, Lucien N.,Ernst, Dani?l,Hopkins, Samantha L.,Meijer, Michael S.,Askes, Sven H. C.,Le Dévédec, Sylvia E.,Bonnet, Sylvestre
, p. 11549 - 11553 (2017)
We describe two water-soluble ruthenium complexes, [1]Cl2 and [2]Cl2, that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21 J cm?2) of red light in an oxyg
Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases
Nathubhai, Amit,Haikarainen, Teemu,Hayward, Penelope C.,Mu?oz-Descalzo, Silvia,Thompson, Andrew S.,Lloyd, Matthew D.,Lehti?, Lari,Threadgill, Michael D.
, p. 316 - 327 (2016/05/19)
Tankyrases (TNKSs), members of the PARP (Poly(ADP-ribose)polymerases) superfamily of enzymes, have gained interest as therapeutic drug targets, especially as they are involved in the regulation of Wnt signalling. A series of 2-arylquinazolin-4-ones with varying substituents at the 8-position was synthesised. An 8-methyl group (compared to 8-H, 8-OMe, 8-OH), together with a 4′-hydrophobic or electron-withdrawing group, provided the most potency and selectivity towards TNKSs. Co-crystal structures of selected compounds with TNKS-2 revealed that the protein around the 8-position is more hydrophobic in TNKS-2 compared to PARP-1/2, rationalising the selectivity. The NAD+-binding site contains a hydrophobic cavity which accommodates the 2-aryl group; in TNKS-2, this has a tunnel to the exterior but the cavity is closed in PARP-1. 8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one was identified as a potent and selective inhibitor of TNKSs and Wnt signalling. This compound and analogues could serve as molecular probes to study proliferative signalling and for development of inhibitors of TNKSs as drugs.
Heteroarylacetic phenylbenzamide, composition and method of use (by machine translation)
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Paragraph 0177, (2016/10/08)
Provided are certain heteroaryl benzamides, compositions, and methods of their manufacture and use.