Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma
Publication Date
July 19, 2016
Journal
PLOS ONE
Authors
Bonnie K. Harrington, Heather L. Gardner, Raquel Izumi, Ahmed Hamdy, et al
Volume
11
Issue
7
Pages
e0159607
DOI
https://dx.plos.org/10.1371/journal.pone.0159607
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0159607
Web of Science
000380169600076
Scopus
84979239943
Mendeley
http://www.mendeley.com/research/preclinical-evaluation-novel-btk-inhibitor-acalabrutinib-canine-models-bcell-nonhodgkin-lymphoma
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Mendeley | Further Information

{"title"=>"Preclinical evaluation of the novel BTK inhibitor acalabrutinib in canine models of B-cell non-hodgkin lymphoma", "type"=>"journal", "authors"=>[{"first_name"=>"Bonnie K.", "last_name"=>"Harrington", "scopus_author_id"=>"55987489800"}, {"first_name"=>"Heather L.", "last_name"=>"Gardner", "scopus_author_id"=>"56611436900"}, {"first_name"=>"Raquel", "last_name"=>"Izumi", "scopus_author_id"=>"55541758100"}, {"first_name"=>"Ahmed", "last_name"=>"Hamdy", "scopus_author_id"=>"39961570900"}, {"first_name"=>"Wayne", "last_name"=>"Rothbaum", "scopus_author_id"=>"57076983400"}, {"first_name"=>"Kevin R.", "last_name"=>"Coombes", "scopus_author_id"=>"6701706213"}, {"first_name"=>"Todd", "last_name"=>"Covey", "scopus_author_id"=>"57076154800"}, {"first_name"=>"Allard", "last_name"=>"Kaptein", "scopus_author_id"=>"7005536009"}, {"first_name"=>"Michael", "last_name"=>"Gulrajani", "scopus_author_id"=>"55546251900"}, {"first_name"=>"Bart", "last_name"=>"Van Lith", "scopus_author_id"=>"57196008099"}, {"first_name"=>"Cecile", "last_name"=>"Krejsa", "scopus_author_id"=>"6602114385"}, {"first_name"=>"Christopher C.", "last_name"=>"Coss", "scopus_author_id"=>"8912566800"}, {"first_name"=>"Duncan S.", "last_name"=>"Russell", "scopus_author_id"=>"55362142800"}, {"first_name"=>"Xiaoli", "last_name"=>"Zhang", "scopus_author_id"=>"23993074500"}, {"first_name"=>"Bridget K.", "last_name"=>"Urie", "scopus_author_id"=>"16432972600"}, {"first_name"=>"Cheryl A.", "last_name"=>"London", "scopus_author_id"=>"7004400818"}, {"first_name"=>"John C.", "last_name"=>"Byrd", "scopus_author_id"=>"35377719400"}, {"first_name"=>"Amy J.", "last_name"=>"Johnson", "scopus_author_id"=>"24769524900"}, {"first_name"=>"William C.", "last_name"=>"Kisseberth", "scopus_author_id"=>"6602190487"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84979239943", "pmid"=>"27434128", "pui"=>"611323568", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "scopus"=>"2-s2.0-84979239943", "doi"=>"10.1371/journal.pone.0159607", "issn"=>"19326203"}, "id"=>"63be08fb-7028-3cca-9052-90ae20829270", "abstract"=>"Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL).", "link"=>"http://www.mendeley.com/research/preclinical-evaluation-novel-btk-inhibitor-acalabrutinib-canine-models-bcell-nonhodgkin-lymphoma", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>1, "Veterinary Science and Veterinary Medicine"=>3, "Business, Management and Accounting"=>1, "Chemistry"=>6, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>6}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>3}}, "group_count"=>1}

Scopus | Further Information

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