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Design and Discovery of 2‑Arylquinazolin-4-ones as Potent and Selective Inhibitors of Tankyrases

Nathubhai, Amit, Wood, P.J., Lloyd, M.D., Thompson, A.S. and Threadgill, M.D. (2013) Design and Discovery of 2‑Arylquinazolin-4-ones as Potent and Selective Inhibitors of Tankyrases. ACS Medicinal Chemistry Letters, 4 (12). pp. 1173-1177. ISSN 1948-5875

Item Type: Article


Tankyrases (TNKSs) are poly(ADP-ribose)polymerases
(PARPs) that are overexpressed in several clinical cancers. They regulate elongation of telomeres, regulate the Wnt system, and are essential for the function of the mitotic spindle. A set of 2-arylquinazolin-4-ones has been
designed and identified as potent and selective TNKS inhibitors, some being more potent and selective than the lead inhibitor XAV939, with IC50 = 3 nM vs. TNKS-2. Methyl was preferred at the 8-position and modest bulk at the 4-position of the 2-phenyl group; electronic effects and H-bonding were irrelevant, but charge in the 4′-substituent must be avoided. Molecular modeling facilitated initial design of the compounds and rationalization of the SAR of binding into the nicotinamide-binding site of the target enzymes. These compounds have potential for further
development into anticancer drugs.

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Depositing User: Amit Nathubhai


Item ID: 9792
Identification Number:
ISSN: 1948-5875
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Date Deposited: 10 Aug 2018 10:46
Last Modified: 18 Dec 2019 16:07


Author: Amit Nathubhai
Author: P.J. Wood
Author: M.D. Lloyd
Author: A.S. Thompson
Author: M.D. Threadgill

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences


Sciences > Chemistry

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