Tricia J Vos

Publications (6)27.58 Total impact

• Article: Design and optimization of potent and orally bioavailable tetrahydronaphthalene Raf inhibitors.

  Alexandra E Gould, Ruth Adams, Sharmila Adhikari, Kathleen Aertgeerts, Roushan Afroze, Christopher Blackburn, Emily F Calderwood, Ryan Chau, Jouhara Chouitar, Matthew O Duffey, [......], Tricia J Vos, Stepan Vyskocil, Juliet Williams, Tianlin Xu, Johnny J Yang, Jason Yano, Hongbo Zeng, Dong Mei Zhang, Qin Zhang, Katherine M Galvin
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  ABSTRACT: Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.
  Journal of Medicinal Chemistry 02/2011; 54(6):1836-46. · 4.80 Impact Factor
• Article: Discovery and optimization of pyrazoline compounds as B-Raf inhibitors.

  Matthew O Duffey, Ruth Adams, Christopher Blackburn, Ryan W Chau, Susan Chen, Katherine M Galvin, Khristofer Garcia, Alexandra E Gould, Paul D Greenspan, Sean Harrison, [......], Jane X Liu, Li-Ting Ma, Saurabh Menon, Masayuki Nagayoshi, R Scott Rowland, Tricia J Vos, Tianlin Xu, Johnny J Yang, Shaoxia Yu, Qin Zhang
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  ABSTRACT: The discovery of novel pyrazoline derivatives as B-Raf (V600E) inhibitors is described in this report. Chemical modification of the pyrazoline scaffold led to the development of SAR and identified potent and selective inhibitors of B-Raf (V600E). Determination of the pharmacokinetic properties of selected inhibitors is also reported.
  Bioorganic & medicinal chemistry letters 08/2010; 20(16):4800-4. · 2.65 Impact Factor
• Article: Discovery and optimization of N-acyl and N-aroylpyrazolines as B-Raf kinase inhibitors.

  Christopher Blackburn, Matthew O Duffey, Alexandra E Gould, Bheemashankar Kulkarni, Jane X Liu, Saurabh Menon, Masayuki Nagayoshi, Tricia J Vos, Juliet Williams
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  ABSTRACT: A high throughput screen identified N-aroylpyrazoline 1 as a selective inhibitor of the V600E mutant of B-Raf kinase. Parallel synthesis of acyl, aroyl, and sulfonyl derivatives led to the identification of several potent inhibitors in both enzymatic and cellular (pERK) assays such as compound 42.
  Bioorganic & medicinal chemistry letters 08/2010; 20(16):4795-9. · 2.65 Impact Factor
• Source

  Available from: pnas.org

  Article: Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase.

  Mark G Manfredi, Jeffrey A Ecsedy, Kristan A Meetze, Suresh K Balani, Olga Burenkova, Wei Chen, Katherine M Galvin, Kara M Hoar, Jessica J Huck, Patrick J LeRoy, Emily T Ray, Todd B Sells, Bradley Stringer, Stephen G Stroud, Tricia J Vos, Gabriel S Weatherhead, Deborah R Wysong, Mengkun Zhang, Joseph B Bolen, Christopher F Claiborne
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  ABSTRACT: Increased Aurora A expression occurs in a variety of human cancers and induces chromosomal abnormalities during mitosis associated with tumor initiation and progression. MLN8054 is a selective small-molecule Aurora A kinase inhibitor that has entered Phase I clinical trials for advanced solid tumors. MLN8054 inhibits recombinant Aurora A kinase activity in vitro and is selective for Aurora A over the family member Aurora B in cultured cells. MLN8054 treatment results in G(2)/M accumulation and spindle defects and inhibits proliferation in multiple cultured human tumor cells lines. Growth of human tumor xenografts in nude mice was dramatically inhibited after oral administration of MLN8054 at well tolerated doses. Moreover, the tumor growth inhibition was sustained after discontinuing MLN8054 treatment. In human tumor xenografts, MLN8054 induced mitotic accumulation and apoptosis, phenotypes consistent with inhibition of Aurora A. MLN8054 is a selective inhibitor of Aurora A kinase that robustly inhibits growth of human tumor xenografts and represents an attractive modality for therapeutic intervention of human cancers.
  Proceedings of the National Academy of Sciences 04/2007; 104(10):4106-11. · 9.68 Impact Factor
• Article: Identification and structure-activity relationships of a new series of Melanocortin-4 receptor antagonists.

  Tricia J Vos, Suresh Balani, Christopher Blackburn, Ryan W Chau, M Diana Danca, Stacey V Drabic, Cheryl A Farrer, Michael A Patane, Stephen G Stroud, David L Yowe, Christopher F Claiborne
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  ABSTRACT: The identification and optimization of a series of acylguanidine-based melanocortin-4 receptor antagonists is discussed.
  Bioorganic & Medicinal Chemistry Letters 05/2006; 16(8):2302-5. · 2.55 Impact Factor
• Article: Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model.

  Tricia J Vos, Andrei Caracoti, Jennifer L Che, Mingshi Dai, Cheryl A Farrer, Nancy E Forsyth, Stacey V Drabic, Robert A Horlick, Diana Lamppu, David L Yowe, Suresh Balani, Ping Li, Hang Zeng, Ingrid B J K Joseph, Luis E Rodriguez, Martin P Maguire, Michael A Patane, Christopher F Claiborne
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  ABSTRACT: The melanocortin 4 receptor (MC4R) plays an important role in body weight regulation and energy homeostasis. Administration of peptidic MC4R antagonists (usually by intracerebro ventricular injection) has been shown in the literature to increase body weight and/or food intake in several rodent models. We report here the identification of a novel nonpeptidic MC4R antagonist and its effects on tumor-induced weight loss in mice following peripheral administration.
  Journal of Medicinal Chemistry 04/2004; 47(7):1602-4. · 5.25 Impact Factor