Abstract：
PURPOSE:The growing amount of heterogeneous bioactivity data requires effective strategies to assess the promiscuity/selectivity of small-molecules and aid drug discovery. In the current study, we aim to evaluate the potential of assay profiles (APs, i.e., unique combinations of assay-related features describing how activity determinations were performed and reported) in molecular promiscuity analysis. METHODS:Using PubChem bioactivity data, we computed for all Molecular Libraries Small Molecule Repository (MLSMR library) compounds the frequency of hits score (FoH, i.e., the ratio between the number of times the compound was found active and the number of times it was tested), which were subsequently fit into 32 theoretical APs. The promiscuity of drugs and non-drugs was compared at different levels of test results. RESULTS:We found 8 dominant APs, indicating that compounds tested in more than ten assays (or against ten targets) and found active at least once tend to reach near to maximum hit rates in scientific literature and confirmatory assays (e.g., 95% of the drugs show FoH scores >0.93). Primary and high-throughput screening testing results in very low hit rates (e.g., 95% of the compounds show FoH scores <0.11), promoting a different perspective of promiscuity. In general, drugs exert higher promiscuity compared to non-drugs. Targets and classes of drugs are also discussed within the main APs. CONCLUSION:APs contain relevant features and are suited for big data promiscuity analysis. The activity data of the main APs are freely available on www.chembioinf.ro .
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Avram S,Curpan R,Bora A,Neanu C,Halip Ldoi
10.1007/s11095-018-2523-1subject
Has Abstractpub_date
2018-10-18 00:00:00pages
240issue
11eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-018-2523-1journal_volume
35pub_type
杂志文章abstract：PURPOSE:Studies were conducted to evaluate whether the use of an in vitro model of the blood-brain barrier (BBB) resulted in more accurate predictions of the in vivo transport of compounds compared to the use of a human intestinal cell line (Caco-2). METHODS:The in vitro BBB model employs bovine brain capillary endoth...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016462205267
更新日期：2002-07-01 00:00:00
abstract：PURPOSE:To compare the permeation characteristics of amide bond-containing HIV-1 protease inhibitors and their pyrrolinone-containing counterparts across Caco-2 cell monolayers, a model of the intestinal mucosa. METHODS:Transepithelial transport and cellular uptake of three pairs of amide bond-containing and pyrrolino...
journal_title：Pharmaceutical research
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doi：10.1023/a:1011966918959
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abstract：PURPOSE:To investigate the effect of γ-irradiation of poly(lactic-co-glycolic acid) (PLGA)/Al(OH)₃/0 or 5 wt% diethyl phthalate (DEP) microspheres for active self-healing encapsulation of vaccine antigens. METHODS:Microspheres were irradiated with ⁶⁰Co at 2.5 and 1.8 MRad and 0.37 and 0.20 MRad/h. Encapsulation of tet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1019-2
更新日期：2013-07-01 00:00:00
abstract：:The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vei...
journal_title：Pharmaceutical research
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doi：10.1023/A:1016374508542
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abstract：PURPOSE:To assess the effects of selective lipid extraction and tape stripping on transepidermal water loss (TEWL) at three body regions in the pig. METHODS:Lipids were extracted from the abdominal, inguinal. and back regions using three different solvent extraction procedures or cellophane tape stripping (15x) on Yor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010944529387
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abstract：PURPOSE:The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial gro...
journal_title：Pharmaceutical research
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doi：10.1007/s11095-006-9750-6
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journal_title：Pharmaceutical research
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更新日期：2007-07-01 00:00:00
abstract：PURPOSE:For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of ae...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5277-5
更新日期：2005-08-01 00:00:00
abstract：PURPOSE:Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To addre...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0190-y
更新日期：2010-09-01 00:00:00
abstract：:Aucubin, a promising hepatoprotecting iridoid glucoside, was given intravenously (iv), orally (po), intraperitoneally (ip), and hepatoportally (pv) to rats. A linear pharmacokinetic behavior was obtained after iv administation of 400-400 mg/kg of aucubin. The half-life of aucubin in the postdistributive phase (t1/2, b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015821527621
更新日期：1991-08-01 00:00:00
abstract：PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011936901638
更新日期：1998-06-01 00:00:00
abstract：PURPOSE:One of the major hurdles facing nanomedicines is the antibody production against nanoparticles that subsequently results in their opsonization and clearance by macrophages. The objective of this research was to examine and identify the sequence of a low-immunogenic peptide based on recombinant elastin-like poly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1683-5
更新日期：2015-09-01 00:00:00
abstract：:Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015810312465
更新日期：1992-05-01 00:00:00
abstract：PURPOSE:We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS:Plasma azetire...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012141025938
更新日期：1997-08-01 00:00:00
abstract：PURPOSE:The preparation of drug/cyclodextrin complexes is a suitable method to improve the dissolution of poor soluble drugs. The efficacy of the Controlled Particle Deposition (CPD) as a new developed method to prepare these complexes in a single stage process using supercritical carbon dioxide is therefore compared w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9177-0
更新日期：2007-03-01 00:00:00
abstract：:A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015896121377
更新日期：1991-02-01 00:00:00
abstract：PURPOSE:The gastric mucoadhesive property of tetracycline-sucralfate acidic complex (CO) was evaluated by using a novel method in vitro to compare with the in vivo test. The mucoadhesive mechanism of the acidic complex was also studied. METHODS:The gastric mucosa removed from a rat was placed covering the end of a plu...
journal_title：Pharmaceutical research
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doi：10.1023/B:PHAM.0000019293.57927.7f
更新日期：2004-03-01 00:00:00
abstract：:Interogan variation in tissue distribution of weakly basic drugs such as quinidine, propranolol, and imipramine was investigated as a function of binding to phosphatidylserine (PhS) in tissues. Tissue distributions of these drugs were determined using 10 different tissues at a steady-state plasma concentration and wer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015935031933
更新日期：1990-10-01 00:00:00
abstract：:The release of lithium carbonate incorporated into polymethylmethacrylate, polyvinyl chloride, hydrogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-rel...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015863204732
更新日期：1990-04-01 00:00:00
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更新日期：1998-08-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2013-04-01 00:00:00
abstract：:Leucine enkephalin (YGGFL) undergoes rapid degradation in sheep nasal mucosa to yield GGFL which is further degraded to FL. The activity of the nasal mucosal homogenate against YGGFL and GGFL (t1/2 12 and 7 min) was significantly greater than that observed with a nasal wash fluid (t1/2 40 and 13 min). The effect of cy...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018946829225
更新日期：1994-12-01 00:00:00
abstract：PURPOSE:Development of a human mitochondrial gene delivery vector is a critical step in the ability to treat diseases arising from mutations in mitochondrial DNA. Although we have previously cloned the mouse mitochondrial genome in its entirety and developed it as a mitochondrial gene therapy vector, the human mitochon...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0527-1
更新日期：2011-11-01 00:00:00
abstract：PURPOSE:To test the hypothesis that modification of release pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) formulations shifts gastrointestinal (GI) toxicity of the drugs from the upper GI region to the distal intestine. METHODS:We assessed tiaprofenic acid (TA)-induced upper and lower increased GI permeabil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018887216098
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo. METHODS:Preparation and characte...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2016-12-01 00:00:00
abstract：PURPOSE:This study investigated the penetration of lidocaine around and through a sutured incision following the application of iontophoretic and passive patches in the CD Hairless rat. MATERIALS AND METHODS:Concentrations in localized areas (suture, dermis, subcutaneous, and vascular) were determined using microdialy...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9490-2
更新日期：2008-08-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9514-y
更新日期：2008-07-01 00:00:00
abstract：:The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0397-6
更新日期：2011-07-01 00:00:00
abstract：PURPOSE:The purpose of this study was to investigate the pH-dependent passive and active transport of weakly basic drugs across the human intestinal epithelium. METHODS:The bidirectional pH-dependent transport of weak bases was studied in Caco-2 cell monolayers in the physiologic pH range of the gastrointestinal tract...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1025032511040
更新日期：2003-08-01 00:00:00
