Publications by authors named "Christine M Wood"

4 Publications

  • Page 1 of 1

Discovery and Characterization of AZD6738, a Potent Inhibitor of Ataxia Telangiectasia Mutated and Rad3 Related (ATR) Kinase with Application as an Anticancer Agent.

J Med Chem 2018 11 10;61(22):9889-9907. Epub 2018 Nov 10.

Chemistry, Oncology, IMED Biotech Unit , AstraZeneca , Cambridge Science Park, 310 Milton Road , Milton, Cambridge CB4 0WG , U.K.

The kinase ataxia telangiectasia mutated and rad3 related (ATR) is a key regulator of the DNA-damage response and the apical kinase which orchestrates the cellular processes that repair stalled replication forks (replication stress) and associated DNA double-strand breaks. Inhibition of repair pathways mediated by ATR in a context where alternative pathways are less active is expected to aid clinical response by increasing replication stress. Here we describe the development of the clinical candidate 2 (AZD6738), a potent and selective sulfoximine morpholinopyrimidine ATR inhibitor with excellent preclinical physicochemical and pharmacokinetic (PK) characteristics. Compound 2 was developed improving aqueous solubility and eliminating CYP3A4 time-dependent inhibition starting from the earlier described inhibitor 1 (AZ20). The clinical candidate 2 has favorable human PK suitable for once or twice daily dosing and achieves biologically effective exposure at moderate doses. Compound 2 is currently being tested in multiple phase I/II trials as an anticancer agent.
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http://dx.doi.org/10.1021/acs.jmedchem.8b01187DOI Listing
November 2018

Acculturation among Latino primary caregivers and physician communication: receipt of advice regarding healthy lifestyle behaviors.

J Community Health 2013 Feb;38(1):113-9

Department of Psychology, University of La Verne, La Verne, CA 91750, USA.

The present study was part of a larger randomized controlled childhood obesity prevention trial based in 11 public recreation centers. The primary aim was to evaluate the effectiveness of a multi-level intervention to prevent the onset of overweight and obesity among children (5-8 years of age). However, the purpose of the current study was to identify sociodemographic variables, such as acculturation, that were associated with receipt of physician advice among Latino primary caregivers. Participants included 221 Latino primary caregivers and their children from San Diego, CA. Cross-sectional baseline data suggested that Latino children with private insurance were more likely to receive physician advice regarding their eating habits. Conversely, primary caregivers between the ages of 30-39 were less likely to receive physician advice regarding their child's eating habits. Current findings highlight the continued need to improve preventive efforts and reduce health disparities among a vulnerable population, such as Latinos.
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http://dx.doi.org/10.1007/s10900-012-9588-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779273PMC
February 2013

Selective non zinc binding inhibitors of MMP13.

Bioorg Med Chem Lett 2011 Jul 27;21(14):4215-9. Epub 2011 May 27.

AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

Directed screening has identified a novel series of MMP13 inhibitors that possess good levels of activity whilst possessing excellent selectivity over related MMPs. The binding mode of the series has been solved by co-crystallisation and demonstrates an interesting mode of inhibition without interaction with the catalytic zinc atom.
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http://dx.doi.org/10.1016/j.bmcl.2011.05.075DOI Listing
July 2011

Novel inhibitors of the alphavbeta3 integrin--lead identification strategy.

Bioorg Med Chem Lett 2009 Aug 13;19(16):4832-5. Epub 2009 Jun 13.

AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

A novel approach to inhibition of the alphavbeta3 integrin is described, which uses compounds designed to generate nM potency without using the arginine binding site.
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http://dx.doi.org/10.1016/j.bmcl.2009.06.041DOI Listing
August 2009