Abstract:
:Regorafenib is a small molecule inhibitor of tyrosine kinases, and has been shown to improve the outcomes of patients with advanced colorectal cancer and advanced gastrointestinal stromal tumors. The transport profiles of regorafenib by various transporters were evaluated. HEK293/organic anion transporting polypeptide 1B1 (OATP1B1) cells exhibited increased drug sensitivity to regorafenib. Regorafenib inhibited the uptake of 3H-estrone sulfate by HEK293/OATP1B1 cells in a dose-dependent manner, but did not affect its elimination by P-glycoproteins. The concentration of regorafenib was significantly lower in LLC-PK1/multidrug resistance protein 2 (MRP2) cells than in LLC-PK1 cells treated with the MRP2 inhibitor, MK571. MK571 abolished the inhibitory effects of regorafenib on intracellular accumulation in LLC-PK1/MRP2 cells. The uptake of regorafenib was significantly higher in HEK293/OATP1B1 cells than in OATP1B1-mock cells. Transport kinetics values were estimated to be Km=15.9 µM and Vmax=1.24 nmol/mg/min. No significant difference was observed in regorafenib concentrations between HEK293/OATP1B3 and OATP1B3-mock cells. These results indicated that regorafenib is a substrate for MRP2 and OATP1B1, and also suggest that the substrate preference of regorafenib may implicate the pharmacokinetic profiles of regorafenib.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Ohya H,Shibayama Y,Ogura J,Narumi K,Kobayashi M,Iseki Kdoi
10.1248/bpb.b14-00740subject
Has Abstractpub_date
2015-01-01 00:00:00pages
582-6issue
4eissn
0918-6158issn
1347-5215journal_volume
38pub_type
杂志文章abstract::In a previous study, we reported that one of the gel-forming (1-->3)-beta-D-glucans, grifolan (from Grifola frondosa, GRN), stimulated cytokine production from macrophages in vitro. However, several other gel-forming (1-->3)-beta-D-glucans, such as sonifilan (SPG) and SSG, did not induce cytokine production from macro...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.1320
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.1607
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.21.924
更新日期:1998-09-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.903
更新日期:1995-06-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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pub_type: 杂志文章
doi:10.1248/bpb.26.1681
更新日期:2003-12-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.24.1263
更新日期:2001-11-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.20.168
更新日期:1997-02-01 00:00:00
abstract::Middle East Respiratory Syndrome Coronavirus (MERS CoV) is a new emerging viral disease characterized by high fatality rate. Understanding MERS CoV genetic aspects and codon usage pattern is important to understand MERS CoV survival, adaptation, evolution, resistance to innate immunity, and help in finding the unique ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00241
更新日期:2017-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.105
更新日期:2006-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.1736
更新日期:2005-09-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.17.715
更新日期:1994-05-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.21.784
更新日期:1998-07-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2002-12-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.1504
更新日期:2006-07-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b17-00091
更新日期:2017-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.21.1187
更新日期:1998-11-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b14-00517
更新日期:2015-01-01 00:00:00
abstract::Fraxinellone and sauchinone, isolated from natural substance, are known to have an anti-inflammatory effect in inflammatory conditions. However, the anti-inflammatory actions of these compounds have been insufficiently demonstrated in viral-induced neuroinflammation. A viral component (double-stranded (ds)RNA) trigger...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.1870
更新日期:2009-11-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.34.389
更新日期:2011-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.33.22
更新日期:2010-01-01 00:00:00
abstract::Manganese (Mn) plays an important role in the etiology of several neurobehavioral disorders, but there is a lack of data regarding its specific effects on neurotransduction, especially dopaminergic neurotransduction. We investigated the relationship between motor deficits and alterations in the expression of tyrosine ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.31.1894
更新日期:2008-10-01 00:00:00
abstract::Biomacromolecules (>40 kDa) have been developed as drug delivery system (DDS) carriers of low-molecular weight drugs to promote these drugs' uptake by cancer tissues via enhanced permeability and retention (EPR) effects. Human serum albumin (HSA) has been found to accumulate in cancer tissues via this EPR effect. HSA ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b16-00867
更新日期:2017-01-01 00:00:00
abstract::This study was conducted to demonstrate the inhibitory effect of saucerneol G (SG), a new lignan, isolated from the aerial part of Saururus chinensis (Saururaceae) on lipopolysaccharide (LPS)-stimulated matrix metalloproteinase-9 (MMP)-9 inductions in RAW 264.7 cells. Aimed at evaluating the mechanism of action by whi...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.33.1944
更新日期:2010-01-01 00:00:00