Pyrimidinone nicotinamide mimetics as selective tankyrase and Wnt pathway inhibitors suitable for in vivo pharmacology

ACS Medicinal Chemistry Letters

Volumn 6, Issue 3, 2015, Pages 254-259

  Johannes, Jeffrey W ^a   Almeida, Lynsie ^a   Barlaam, Bernard ^a   Boriack Sjodin, P Ann ^a   Casella, Robert ^a   Croft, Rosemary A ^a   Dishington, Allan P ^a   Gingipalli, Lakshmaiah ^a   Gu, Chungang ^a   Hawkins, Janet L ^a   Holmes, Jane L ^a   Howard, Tina ^a   Huang, Jian ^a   Ioannidis, Stephanos ^a   Kazmirski, Steven ^a   Lamb, Michelle L ^a   McGuire, Thomas M ^a   Moore, Jane E ^a   Ogg, Derek ^a   Patel, Anil ^a   Pike, Kurt G ^a   Pontz, Timothy ^a   Robb, Graeme R ^a   Su, Nancy ^a   Wang, Haiyun ^a   Wu, Xiaoyun ^a   Zhang, Hai Jun ^a   Zhang, Yue ^a   Zheng, Xiaolan ^a   Wang, Tao ^a   more..

^a ASTRAZENECA   (United Kingdom)

Author keywords

Caco2; oncogenesis; PARP; pharmacokinetics; tankyrase; Wnt

Indexed keywords

7,8 DIHYDRO 2 [4 (TRIFLUOROMETHYL)PHENYL] 5H THIOPYRANO[4,3 D]PYRIMIDIN 4 OL; ANTINEOPLASTIC AGENT; APC PROTEIN; AXIN; AZ 6102; BETA CATENIN; NICOTINAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 2; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 6; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; TANKYRASE; TANKYRASE INHIBITOR; UNCLASSIFIED DRUG; WNT PROTEIN;

ANIMAL EXPERIMENT; ARTICLE; CANCER RESISTANCE; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; GERMLINE MUTATION; IC50; LIPOPHILICITY; NONHUMAN; PHARMACOKINETICS; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; RAT; WNT SIGNALING PATHWAY;

EID: 84924666073     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml5003663     Document Type: Article

References (21)

1. Anastas, J. N.; Moon, R. T. WNT signalling pathways as therapeutic targets in cancer Nat. Rev. Cancer 2013, 13, 11-26
2. Pinto, D.; Gregorieff, A.; Begthel, H.; Clevers, H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium Genes Dev. 2003, 17, 1709-13
3. Segditsas, S.; Tomlinson, I. Colorectal cancer and genetic alterations in the Wnt pathway Oncogene 2006, 25, 7531-7
4. Clevers, H. Wnt/beta-catenin signaling in development and disease Cell 2006, 127, 469-80
5. Markowitz, S. D.; Bertagnolli, M. M. Molecular origins of cancer: Molecular basis of colorectal cancer N. Engl. J. Med. 2009, 361, 2449-60
6. Voronkov, A.; Krauss, S. Wnt/beta-catenin signaling and small molecule inhibitors Curr. Pharm. Des. 2013, 19, 634-64
7. Kahn, M. Can we safely target the WNT pathway? Nat. Rev. Drug. Discovery 2014, 13, 513-32
8. Huang, S. M.; Mishina, Y. M.; Liu, S.; Cheung, A.; Stegmeier, F.; Michaud, G. A.; Charlat, O.; Wiellette, E.; Zhang, Y.; Wiessner, S.; Hild, M.; Shi, X.; Wilson, C. J.; Mickanin, C.; Myer, V.; Fazal, A.; Tomlinson, R.; Serluca, F.; Shao, W.; Cheng, H.; Shultz, M.; Rau, C.; Schirle, M.; Schlegl, J.; Ghidelli, S.; Fawell, S.; Lu, C.; Curtis, D.; Kirschner, M. W.; Lengauer, C.; Finan, P. M.; Tallarico, J. A.; Bouwmeester, T.; Porter, J. A.; Bauer, A.; Cong, F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling Nature 2009, 461, 614-20
9. Rouleau, M.; Patel, A.; Hendzel, M. J.; Kaufmann, S. H.; Poirier, G. G. PARP inhibition: PARP1 and beyond Nat. Rev. Cancer 2010, 10, 293-301
10. Smith, S.; Giriat, I.; Schmitt, A.; de Lange, T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres Science 1998, 282, 1484-7
11. Chang, P.; Coughlin, M.; Mitchison, T. J. Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function Nat. Cell Biol. 2005, 7, 1133-9
12. Lehtiö, L.; Chi, N. W.; Krauss, S. Tankyrases as drug targets FEBS J. 2013, 280, 3576-93
13. Haikarainen, T.; Krauss, S.; Lehtio, L. Tankyrases: structure, function and therapeutic implications in cancer Curr. Pharm. Des. 2014, 20, 6472-88
14. Liscio, P.; Carotti, A.; Asciutti, S.; Karlberg, T.; Bellocchi, D.; Llacuna, L.; Macchiarulo, A.; Aaronson, S. A.; Schüler, H.; Pellicciari, R.; Camaioni, E. Design, synthesis, crystallographic studies, and preliminary biological appraisal of new substituted triazolo[4,3-b]pyridazin-8-amine derivatives as tankyrase inhibitors J. Med. Chem. 2014, 57, 2807-12
15. Lau, T.; Chan, E.; Callow, M.; Waaler, J.; Boggs, J.; Blake, R. A.; Magnuson, S.; Sambrone, A.; Schutten, M.; Firestein, R.; Machon, O.; Korinek, V.; Choo, E.; Diaz, D.; Merchant, M.; Polakis, P.; Holsworth, D. D.; Krauss, S.; Costa, M. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth Cancer Res. 2013, 73, 3132-44
16. Nathubhai, A.; Wood, P. J.; Lloyd, M. D.; Thompson, A. S.; Threadgill, M. D. Design and Discovery of 2-Arylquinazolin-4-ones as Potent and Selective Inhibitors of Tankyrases ACS Med. Chem. Lett. 2013, 4, 1173-7
17. Haikarainen, T.; Koivunen, J.; Narwal, M.; Venkannagari, H.; Obaji, E.; Joensuu, P.; Pihlajaniemi, T.; Lehtiö, L. para-Substituted 2-phenyl-3,4-dihydroquinazolin-4-ones as potent and selective tankyrase inhibitors ChemMedChem 2013, 8, 1978-85
18. Lehtiö, L.; Collins, R.; van den Berg, S.; Johansson, A.; Dahlgren, L. G.; Hammarström, M.; Helleday, T.; Holmberg-Schiavone, L.; Karlberg, T.; Weigelt, J. Zinc binding catalytic domain of human tankyrase 1 J. Mol. Biol. 2008, 379, 136-45
19. Lovering, F.; Bikker, J.; Humblet, C. Escape from flatland: increasing saturation as an approach to improving clinical success J. Med. Chem. 2009, 52, 6752-6
20. Tuncel, H.; Tanaka, S.; Oka, S.; Nakai, S.; Fukutomi, R.; Okamoto, M.; Ota, T.; Kaneko, H.; Tatsuka, M.; Shimamoto, F. PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development Int. J. Oncol. 2012, 41, 2079-86
21. Tai, W.; Quackenbush, K.; Purkey, A.; Bagby, S.; Messersmith, W.; Song, E.; Pitts, T.; Arcaroli, J. KRAS wild type tumors exhibit increased efficacy to the combination of AZ1 (a tankyrase inhibitor) + irinotecan in a patient-derived CRC explant model. In Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 19-23, 2013; AACR: Philadelphia, PA, 2013; Vol. 12 (11 Suppl), Abstract nr B30.