Abstract:
:Organic anion transporting polypeptides 1B1 and 1B3 are transporters selectively expressed on the basolateral membrane of the hepatocyte. Several studies reveal that they are involved in drug-drug interactions, cancer, and hyperbilirubinemia. In this study, we developed a set of classification models for OATP1B1 and 1B3 inhibition based on more than 1700 carefully curated compounds from literature, which were validated via cross-validation and by use of an external test set. After combining several sets of descriptors and classifiers, the 6 best models were selected according to their statistical performance and were used for virtual screening of DrugBank. Consensus scoring of the screened compounds resulted in the selection and purchase of nine compounds as potential dual inhibitors and of one compound as potential selective OATP1B3 inhibitor. Biological testing of the compounds confirmed the validity of the models, yielding an accuracy of 90% for OATP1B1 and 80% for OATP1B3, respectively. Moreover, at least half of the new identified inhibitors are associated with hyperbilirubinemia or hepatotoxicity, implying a relationship between OATP inhibition and these severe side effects.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Kotsampasakou E,Brenner S,Jäger W,Ecker GFdoi
10.1021/acs.molpharmaceut.5b00583subject
Has Abstractpub_date
2015-12-07 00:00:00pages
4395-404issue
12eissn
1543-8384issn
1543-8392journal_volume
12pub_type
杂志文章abstract::Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300277f
更新日期:2012-08-06 00:00:00
abstract::In vitro antibody discovery and/or affinity maturation are often performed using antibody fragments (Fabs), but most monovalent Fabs are reformatted as bivalent IgGs (monoclonal antibodies, mAbs) for therapeutic applications. One problem related to reformatting antibodies is that the bivalency of mAbs can lead to incr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00779
更新日期:2018-01-02 00:00:00
abstract::Most vaccines contain aluminum adjuvants; however, their exact mechanism of action remains unclear. A novel mechanism by Shi and colleagues proposes aluminum adjuvants may enhance immune activation by binding and reorganizing lipids that are key components of lipid rafts. To better understand the specificity of intera...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00111
更新日期:2016-05-02 00:00:00
abstract::Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Sin...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00355
更新日期:2017-09-05 00:00:00
abstract::Currently, the most prominent barrier to the success of orally delivered paclitaxel (PTX) is the extremely limited bioavailability of delivered therapeutic. In light of this issue, an amphiphilic sulfhydrylated N-deoxycholic acid-N,O-hydroxyethyl chitosan (TGA-DHC) was synthesized to improve the oral bioavailability o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00662
更新日期:2017-12-04 00:00:00
abstract::In our previous studies, ethylene glycol-linked amino acid diester prodrugs of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug, designed to target peptide transporter 1 (PepT1) have been synthesized and evaluated. Unlike ethylene glycol, propylene glycol is of very low toxicity in viv...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300647m
更新日期:2013-04-01 00:00:00
abstract::There is a great need for delivery strategies capable of efficiently localizing drugs to the damaged myocardium that do not require direct intramyocardial injection of therapeutic molecules. In the work discussed here, we exploited the myocardium-specific upregulation of matrix metalloproteinases (MMPs) that occurs du...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500653y
更新日期:2015-04-06 00:00:00
abstract::The ATP-binding cassette (ABC) drug transporter ABCG2 can actively efflux a wide variety of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular accumulation of these drugs. Therefore, the overexpression of ABCG2 often contributes to the development of multidrug resistance (MDR) in can...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00334
更新日期:2017-08-07 00:00:00
abstract::Chemotherapy is an indispensable auxiliary treatment for glioma but highly limited by the existence of both blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). The dysfunctional brain tumor blood vessels and high interstitial pressure in glioma also greatly hindered the accumulation and deep penetration of...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400189j
更新日期:2014-01-06 00:00:00
abstract::Near-infrared (NIR)-to-visible upconversion nanoparticle (UCNP) has shown promising prospects in photodynamic therapy (PDT) as a drug carrier or energy donor. In this work, a photosensitizer pyropheophorbide a (Ppa) and RGD peptide c(RGDyK) comodified chitosan-wrapped NaYF(4):Yb/Er upconversion nanoparticle UCNP-Ppa-R...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200590y
更新日期:2012-06-04 00:00:00
abstract::High-functionality and -quality (HFQ) lipids have a discrete molecular weight and good water dispersibility and can be produced by solid-phase peptide synthesis. Therefore, HFQ lipids are a promising material for the preparation of ligand-grafted PEGylated liposomes. Recently, we have reported serine-glycine repeated ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00476
更新日期:2018-10-01 00:00:00
abstract::The small molecule fluorescein is commonly used to guide the repair of cerebral spinal fluid leaks (CSFLs) in the clinic. We modified fluorescein so that it is also visible by positron emission tomography (PET). This probe was used to quantitatively track the fast distribution of small molecules in the CSF of rats. We...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00485
更新日期:2019-08-05 00:00:00
abstract::The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phot...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp5001923
更新日期:2014-06-02 00:00:00
abstract::Amino acids derivative are well established molecular probes for diagnosis of a variety of cancer using positron emission tomography (PET). Recently, boramino acid (BAAs) was found as a prospective molecular platform for developing PET tracer. The objective of this study was to develop a 18F-labeled alanine derivative...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00884
更新日期:2018-03-05 00:00:00
abstract::Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-asse...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00349
更新日期:2019-09-03 00:00:00
abstract::In this paper, we investigate the release of two drugs, nicotine and caffeine, from poly epsilon-caprolactone (PCL) matrices, as a model for the delivery of highly hydrophilic drugs. Since PCL does not degrade over the period of our experiments (<30 days), drug diffusion through the matrix is expected to be the domina...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp700097x
更新日期:2007-11-01 00:00:00
abstract::Targeted delivery of anticancer drugs to brain tumors, especially glioblastoma multiforme, which is the most frequent and aggressive type, is one of the important objectives in nanomedicine. Vascular endothelial growth factor (VEGF) and its receptor type II (VEGFR2) are promising targets because they are overexpressed...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00519
更新日期:2016-11-07 00:00:00
abstract::Tumor endothelial marker 8 (TEM8) is a cell surface receptor that is highly expressed in a variety of human tumors and promotes tumor angiogenesis and cell growth. Antibodies targeting TEM8 block tumor angiogenesis in a manner distinct from the VEGF receptor pathway. Development of a TEM8 imaging agent could aid in pa...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500056d
更新日期:2014-11-03 00:00:00
abstract::Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs posse...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00670
更新日期:2016-04-04 00:00:00
abstract::Cyclic RGD (cRGD) peptide-conjugated boronated albumin was developed to direct toward integrin αvβ3, which overexpresses on many cancer cells. A stepwise conjugation of c[RGDfK(Mal)] and maleimide-conjugated closo-dodecaborate (MID) to bovine serum albumin (BSA) afforded cRGD-MID-BSA, which was noncytotoxic toward bot...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00478
更新日期:2020-10-05 00:00:00
abstract::Drug transporter expression and function at the blood-brain barrier is altered in Alzheimer's disease (AD). However, the impact of AD on the expression of transporters and metabolizing enzymes in peripheral tissues has received little attention. The current study evaluated the expression of drug transporters and metab...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00500
更新日期:2018-09-04 00:00:00
abstract::Mouse laser-induced choroidal neovascularization (mouse LCNV) recapitulates the "wet" form of human age-related macular degeneration (AMD). Vascular cell adhesion molecule-1 (VCAM-1) is a known inflammatory biomarker, and it increases in the choroidal neovascular tissues characteristic of this experimental model. We h...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00661
更新日期:2018-12-03 00:00:00
abstract::Herein, we elucidated the mechanisms and key factors for the tumor-targeting ability of nanoparticles that presented high targeting efficiency for liver tumor. We used several different nanoparticles with sizes of 200-300 nm, including liposome nanoparticles (LNPs), polystyrene nanoparticles (PNPs) and glycol chitosan...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00507
更新日期:2016-11-07 00:00:00
abstract::We have developed a novel water-dispersible oleic acid (OA)-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents. Drug partitions into the OA shell surrounding iron oxide nanoparticles, and the Pluronic that anchors at the OA-water ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp0500014
更新日期:2005-05-01 00:00:00
abstract::Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO)...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp9001393
更新日期:2010-02-01 00:00:00
abstract::Polymer therapeutics offer potential benefits in the treatment of multidrug resistant (MDR) infections; affording targeted delivery of biologically active agents to the site of inflammation, potential decreases in systemic toxicity, and the retention of antimicrobial activity at the target site. As a prototype model, ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500584u
更新日期:2014-12-01 00:00:00
abstract::Intracellular unbound drug concentrations determine affinity to targets in the cell interior. However, due to difficulties in measuring them, they are often overlooked in pharmacology. Here we present a simple experimental technique for the determination of unbound intracellular drug concentrations in cultured cells t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4000822
更新日期:2013-06-03 00:00:00
abstract::Similar to glycolysis, glutaminolysis acts as a vital energy source in tumor cells, providing building blocks for the metabolic needs of tumor cells. To capture glutaminolysis in tumors, 18F-(2S,4R)4-fluoroglutamine ([18F]FGln) and 18F-fluoroboronoglutamine ([18F]FBQ) have been successfully developed for positron emis...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00891
更新日期:2019-12-02 00:00:00
abstract::Within the immune system there is an exquisite ability to discriminate between "self" and "non-self" that is orchestrated by antigen-specific T lymphocytes. Genomic plasticity enables differentiation of naive CD4+ T lymphocytes into either regulatory cells (Treg) that express the transcription factor Foxp3 and activel...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100203a
更新日期:2011-02-07 00:00:00
abstract::Lipid-core nanocapsules (LCNs) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, it is not clear whether the LCNs carry the drug through the blood-brain barrier or increase free drug penetration due to changes in the barrier permeability. Quetiapine (QTP) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00875
更新日期:2016-04-04 00:00:00