نتایج جستجو برای: alisertib

تعداد نتایج: 124  

2016
Gerald S. Falchook Xiaofei Zhou Karthik Venkatakrishnan Razelle Kurzrock Devalingam Mahalingam Jonathan W. Goldman JungAh Jung Claudio Dansky Ullmann Catherine Milch Lee S. Rosen John Sarantopoulos

OBJECTIVE This study was conducted to characterize the effects of food on single-dose pharmacokinetics (PK) of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. METHODS Following overnight fasting for 10 h, a single 50 mg enteric-coated tablet (ECT) of alisertib was administered under either fasted (alisertib with 240 mL of water) or fed...

Journal: :Molecular cancer therapeutics 2015
Brian Gabrielli Fawzi Bokhari Max V Ranall Zay Yar Oo Alexander J Stevenson Weili Wang Melanie Murrell Mushfiq Shaikh Sora Fallaha Daniel Clarke Madison Kelly Karin Sedelies Melinda Christensen Sara McKee Graham Leggatt Paul Leo Dubravka Skalamera H Peter Soyer Thomas J Gonda Nigel A J McMillan

Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selecti...

2018
Xiaofei Zhou Diane R Mould Takatoshi Takubo Emily Sheldon-Waniga Dirk Huebner Ashley Milton Karthik Venkatakrishnan

AIMS This population pharmacokinetic analysis was conducted to describe quantitatively the regional differences and sources of interpatient variability on the apparent oral clearance of alisertib. METHODS A population pharmacokinetic analysis was performed on data from 671 cancer patients in Western countries and in Japan/East Asia to whom alisertib 5-150 mg once or twice daily (b.i.d.) was a...

2017
Huifeng Niu Hyunjin Shin Feng Gao Jacob Zhang Brittany Bahamon Hadi Danaee Bohuslav Melichar Russell J. Schilder Robert L. Coleman Gerald Falchook Antoine Adenis Kian Behbakht Angela DeMichele Elizabeth Claire Dees Kimberly Perez Ursula Matulonis Piotr Sawrycki Dirk Huebner Jeffrey Ecsedy

BACKGROUND Alisertib (MLN8237) is an investigational, oral, selective Aurora A kinase inhibitor. Aurora A contains two functional single nucleotide polymorphisms (SNPs; codon 31 [F/I] and codon 57 [V/I]) that lead to functional changes. This study investigated the prognostic and predictive significance of these SNPs. METHODS This study evaluated associations between Aurora A SNPs and overall ...

Journal: :Molecular cancer therapeutics 2015
John J Tentler Anastasia A Ionkina Aik Choon Tan Timothy P Newton Todd M Pitts Magdalena J Glogowska Peter Kabos Carol A Sartorius Kelly D Sullivan Joaquin M Espinosa S Gail Eckhardt Jennifer R Diamond

Triple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis. Advances in the treatment of TNBC have been hampered by the lack of novel effective targeted therapies. The primary goal of this study was to evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of mitosis, in TNBC models. A secondary objective was to determine the role of the p53 family o...

2015
John J. Tentler Anastasia A. Ionkina Aik Choon Tan Timothy P. Newton Todd M. Pitts Magdalena J. Glogowska Peter Kabos Carol A. Sartorius Kelly D. Sullivan Joaquin M. Espinosa S. Gail Eckhardt Jennifer R. Diamond

Triple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis. Advances in the treatment of TNBC have been hampered by the lack of novel effective targeted therapies. The primary goal of this study was to evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of mitosis, in TNBC models. A secondary objective was to determine the role of the p53 family o...

The high level of conservation in ATP-binding sites of protein kinases increasingly demandsthe quest to find selective inhibitors with little cross reactivity. Kinase kinases are a recently discovered group of Kinases found to be involved in several mitotic events. These proteins represent attractive targets for cancer therapy with several small molecule inhibitors undergoing different ph...

2015
Brian Gabrielli Fawzi Bokhari Max V. Ranall Zay Yar Oo Alexander J. Stevenson Weili Wang Melanie Murrell Mushfiq Shaikh Sora Fallaha Daniel Clarke Karin Sedelies Melinda Christensen Sara McKee Graham Leggatt Paul Leo Dubravka Skalamera H. Peter Soyer Thomas J. Gonda Nigel A.J. McMillan

Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selecti...

2017
Amir T. Fathi Seth A. Wander Traci M. Blonquist Andrew M. Brunner Philip C. Amrein Jeffrey Supko Nicole M. Hermance Amity L. Manning Hossein Sadrzadeh Karen K. Ballen Eyal C. Attar Timothy A. Graubert Gabriela Hobbs Christelle Joseph Ashley M. Perry Meghan Burke Regina Silver Julia Foster Meghan Bergeron Aura Y. Ramos Tina T. Som Kaitlyn M. Fishman Kristin L. McGregor Christine Connolly Donna S. Neuberg Yi-Bin Chen

Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received ...

Journal: :Nature Reviews Urology 2018

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