Kinact: Maximal rate of enzyme inactivation (time-dependent inhibition) Ko143: (3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)- 1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester LLC-PK1: Porcine kidney cell line MDCKII: Madin-Darby canine kidney II cells OATP: Organic anion transport polypeptide
نویسندگان
چکیده
Division of Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa (P.S.F., B.R.) Division of Drug Metabolism and Pharmacokinetics, Novartis Institute of Biomedical Research, Basel, Switzerland (H.G., H.S., A.J.) Synexa Life Sciences, Montague Gardens, Cape Town, South Africa (P.J.D.) Division of Medical Microbiology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa (P.J.D.) DMD Fast Forward. Published on December 3, 2012 as doi:10.1124/dmd.112.049593
منابع مشابه
The Inhibitor Ko143 Is Not Specific for ABCG2.
Imaging ATP-binding cassette (ABC) transporter activity in vivo with positron emission tomography requires both a substrate and a transporter inhibitor. However, for ABCG2, there is no inhibitor proven to be specific to that transporter alone at the blood-brain barrier. Ko143 [[(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4- b]indol...
متن کاملUse of cassette dosing approach to examine the effects of P-glycoprotein on the brain and cerebrospinal fluid concentrations in wild-type and P-glycoprotein knockout rats.
The study objectives were 1) to test the hypothesis that the lack of P-glycoprotein (P-gp) and the inhibition of breast cancer resistance protein (Bcrp) at the blood-brain barrier after cassette dosing of potent P-gp and Bcrp inhibitors were due to low plasma concentrations of those inhibitors and 2) to examine the effects of P-gp on the unbound brain (C(u,brain)) and cerebrospinal fluid (CSF) ...
متن کاملImpact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032).
Vemurafenib [N-(3-{[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}-2,4-difluorophenyl)propane-1-sulfonamide(PLX4032)] is a novel small-molecule BRAF inhibitor, recently approved by the Food and Drug Administration for the treatment of patients with metastatic melanoma with a BRAF(V600E) mutation. The objective of this study was to investigate the role of P-glycoprotein (P-gp) and br...
متن کاملDmd055590 482..491
The study objectives were 1) to test the hypothesis that the lack of P-glycoprotein (P-gp) and the inhibition of breast cancer resistance protein (Bcrp) at the blood-brain barrier after cassette dosing of potent P-gp and Bcrp inhibitors were due to low plasma concentrations of those inhibitors and 2) to examine the effects of P-gp on the unbound brain (Cu,brain) and cerebrospinal fluid (CSF) co...
متن کاملMolecular pharmacology of ABCG2 and its role in chemoresistance.
The ATP-binding cassette, subfamily G, isoform 2 protein (ABCG2) is an important member of the ABC transporter superfamily, which has been suggested to be involved in multidrug resistance (MDR) in cancer. Its diverse range of substrates includes many common chemotherapeutics such as imatinib, doxorubicin, and mitoxantrone. Physiologically, ABCG2 is highly expressed in areas such as the blood-br...
متن کامل