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Xiaolun Wang,
Dan M Berger,
Edward J Salaski,
Nancy Torres,
Minu Dutia, Cilien Hanna,
Yongbo Hu,
Jeremy I Levin,
Dennis Powell,
Donald Wojciechowicz,
Karen Collins,
Eileen Frommer,
Judy Lucas
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ABSTRACT: Novel indazolylpyrazolo[1,5-a]pyrimidine analogues have been prepared and found to be extremely potent type I B-Raf inhibitors. The lead compound shows good selectivity against a panel of 60 kinases, possesses a desirable pharmacokinetic profile, and demonstrates excellent in vivo antitumor efficacy in B-Raf mutant xenograft models.
Journal of Medicinal Chemistry 10/2010; 53(21):7874-8. · 4.80 Impact Factor
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Edward J Salaski,
Girija Krishnamurthy,
Wei-Dong Ding,
Ker Yu,
Shabana S Insaf,
Clark Eid,
Jaechul Shim,
Jeremy I Levin,
Keiko Tabei,
Lourdes Toral-Barza,
Wei-Guo Zhang,
Leonard A McDonald,
Erick Honores, Cilien Hanna,
Ayako Yamashita,
Bernard Johnson,
Zhong Li,
Leif Laakso,
Dennis Powell,
Tarek S Mansour
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ABSTRACT: The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined. PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.
Journal of Medicinal Chemistry 04/2009; 52(8):2181-4. · 4.80 Impact Factor
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Synthetic Communications 01/2006; 36(4):465-472. · 1.06 Impact Factor
