Daniel J Freeman
Affiliation: Amgen Inc
- Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab aloneDaniel J Freeman
Department of Oncology Research, Amgen Inc, Thousand Oaks, CA 91320, USA
Clin Colorectal Cancer 7:184-90. 2008..Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras, BRAF, and PIK3CA gene mutations with tumor resistance to panitumumab alone...
- Activity of panitumumab alone or with chemotherapy in non-small cell lung carcinoma cell lines expressing mutant epidermal growth factor receptorDaniel J Freeman
Department of Oncology Research, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Mol Cancer Ther 8:1536-46. 2009....
- Synthesis and structure-activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffoldRyan P Wurz
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Bioorg Med Chem Lett 22:5714-20. 2012..Compound 3j also showed a dose dependent reduction in the phosphorylation of Akt in a U87 tumor pharmacodynamic model with a plasma EC(50)=193 nM (91 ng/mL)...
- Selective class I phosphoinositide 3-kinase inhibitors: optimization of a series of pyridyltriazines leading to the identification of a clinical candidate, AMG 511Mark H Norman
Department of Medicinal Chemistry, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320, USA
J Med Chem 55:7796-816. 2012..On the basis of its excellent in vivo efficacy and pharmacokinetic profile, compound 31 was selected for further evaluation as a clinical candidate and was designated AMG 511...
- Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancerRafael G Amado
Amgen, Inc, One Amgen Center Dr, MS 38 2 B, Thousand Oaks, CA 91320 1799, USA
J Clin Oncol 26:1626-34. 2008..Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials...
- Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancerDaniel J Freeman
Amgen Inc, Thousand Oaks, CA, USA
Mol Cancer 11:47. 2012..Successful treatment of solid tumors relies on the ability of drugs to penetrate into the tumor tissue...
- A comparability study of 5 commercial KRAS testsKelly Oliner
Department of Molecular Sciences, Amgen Inc, Thousand Oaks, CA, USA
Diagn Pathol 5:23. 2010..Therefore, an accurate and readily available analysis of KRAS mutational status is needed. The aim of this study was to evaluate concordance between KRAS assays performed by 6 different laboratories...
- Structure-based design of a novel series of potent, selective inhibitors of the class I phosphatidylinositol 3-kinasesAdrian L Smith
Department of Medicinal Chemistry, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, United States
J Med Chem 55:5188-219. 2012..Compound 54 demonstrated a robust PD-PK relationship inhibiting the PI3K/Akt pathway in vivo in a mouse model, and it potently inhibited tumor growth in a U-87 MG xenograft model with an activated PI3K/Akt pathway...
- Azole-based inhibitors of AKT/PKB for the treatment of cancerQingPing Zeng
Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, United States
Bioorg Med Chem Lett 20:1559-64. 2010..One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma...
- Gene expression profiles can predict panitumumab monotherapy responsiveness in human tumor xenograft modelsMichael J Boedigheimer
Amgen Inc, Thousand Oaks, CA 91320, USA
Neoplasia 15:125-32. 2013..We sought to identify a gene array profile that could predict responsiveness to panitumumab, a fully human EGFR-binding antibody, using preclinical models of human cancer...
- Structure-activity relationships of phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors: investigations of various 6,5-heterocycles to improve metabolic stabilityMarkian M Stec
Department of Medicinal Chemistry, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, USA
J Med Chem 54:5174-84. 2011..Imidazopyridazine 10 was found to have similar in vitro potency and in vivo efficacy relative to 1, while only minimal amounts of the corresponding deacetylated metabolite of 10 were observed in hepatocytes...