The estrogen receptor ER-α has been an important target in the pharmaceutical industry for many years, with ER antagonists such as tamoxifen and aromatase inhibitors being key therapeutics in the management of ER-positive breast cancer. GDC-0927 is a novel, potent, orally bioavailable and selective ER-α antagonist with an IC50 value of 0.1 nM and possesses high ER-α degradation efficacy (97%). GDC-0927 displayed an MCF-7 proliferation inhibition with an IC50 value of 0.2 nM. The mouse pharmacokinetic of GDC-0927 is characterized by high clearance (Cl > 60 mL/min/kg) and low bioavailability (%F < 15) and low AUC (po AUC = 0.16 μg•h/mL). GDC-0927 was profiled in a MCF-7 based tamoxifen-resistant xenograft model of breast cancer using subcutaneous estradiol pellets to deliver sufficient levels of estradiol to drive tumor growth. Importantly, GDC-0927 demonstrated high activity with 5 of 8 animals in each cohort showing tumor regressions. Cytochrome P450 inhibition profiling of GDC-0927 indicated it had modest inhibitory effect on CYP2C8 and CYP2C9 (IC50 = 3.0 and 3.2 μM, respectively). When tested for its effect on the hERG channel in a patch clamp assay, GDC-0927 was found to be a moderate inhibitor (IC50 = 4.6 μM)[1].
United States, Massachusetts
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Massachusetts General Hospital.
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, Tennessee
Sarah Cannon Cancer Center
Germantown, Tennessee, United States, 38138
Vanderbilt Ingram Cancer Ctr
Nashville, Tennessee, United States, 37232
Spain
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Onkologikoa - Kutxaren Institutu Onkologikoa
San Sebastian, Guipuzcoa, Spain, 20014
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain, 08035
MD Anderson Cancer Center Madrid - España; Servicio de Farmacia
Madrid, Spain, 28033
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28040
HM Sanchinarro - CIOCC
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010 收起 <<
United States, Massachusetts
... 展开 >>
Massachusetts General Hospital.
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, Tennessee
Sarah Cannon Cancer Center
Germantown, Tennessee, United States, 38138
Vanderbilt Ingram Cancer Ctr
Nashville, Tennessee, United States, 37232
Spain
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Onkologikoa - Kutxaren Institutu Onkologikoa
San Sebastian, Guipuzcoa, Spain, 20014
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain, 08035
MD Anderson Cancer Center Madrid - España; Servicio de Farmacia
Madrid, Spain, 28033
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28040
HM Sanchinarro - CIOCC
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010 收起 <<
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