Disease relevance of Drug Evaluation, Preclinical

• Development of a panel of 15 human ovarian cancer xenografts for drug screening and determination of the role of the glutathione detoxification system [1].
• Drugs known to be topically active in psoriasis, eg, thiotepa, fluorouracil, and betamethasone valerate, were easily detected in the clinical protocol, confirming the validity of this topical drug screening program [2].
• EGFP-expressing HIV-1 could be used for anti-HIV-1 drug screening, sorting of virus-infected cells by fluorescence activated cell sorting (FACS) analysis, and for the rapid and simple detection of virus-infected cells by fluorescence microscopy [3].
• Carbon monoxide (CO)-induced hypoxia in mice: evaluation as an experimental model of cerebral ischemia for drug screening [4].
• In conclusion, screening drug trials show that the ganglionic blocking agent, guanethidine, and competitive tyrosine uptake precursor, alpha-methyl-paratyrosine, effectively blocked dysreflexic hypertension, whereas the beta-blocker, propranolol, did not [5].

High impact information on Drug Evaluation, Preclinical

• The finding that presenilin itself may be the long-sought gamma-secretase, coupled with the recent identification of beta-secretase, has provided discrete biochemical targets for drug screening and development [6].
• The efficacy of preemployment drug screening for marijuana and cocaine in predicting employment outcome [7].
• Drug screenings performed on all patients showed the presence of a cocaine metabolite and the absence of acetaminophen, alcohol, and other potential toxins [8].
• By testing 58 tumor cell lines of the National Cancer Institute's anticancer drug-screening panel for apoptosis sensitivity to S2 and performing death-inducing signaling complex analyses, we determined that half of the CD95-sensitive cells are type I and half are type II [9].
• A native or engineered cysteine in a protein is allowed to react reversibly with a small library of disulfide-containing molecules ( approximately 1,200 compounds) at concentrations typically used in drug screening (10 to 200 microM) [10].

Chemical compound and disease context of Drug Evaluation, Preclinical

• We have used a human tumor clonogenic assay (HTCA) as a disease-oriented drug screening model for new antitumor drugs, in order to test the antitumor activity of 254-S against non-small cell lung carcinoma (NSCLC) and to compare its activity with that of cisplatin (CDDP) and of carboplatin (CBDCA) [11].

Biological context of Drug Evaluation, Preclinical

• The aim of this study is to provide transgenic Drosophila expressing either full-length or truncated forms of human APC (hAPC) protein and methods for using them in functional genomics and drug screening [12].
• Many clinical and forensic toxicology laboratories establish criteria for identifying a random urine specimen submitted for drug screening as being "normally concentrated" or "dilute" by incorporating creatinine analysis and/or specific gravity measurement into their testing protocols [13].
• This concept is supported by the discovery through drug screening of thiazolidinediones (troglitazone, rosiglitazone), compounds that are not only ligands for PPARgamma, a nuclear receptor involved in adipogenesis, but also are antidiabetic agents [14].
• The ability to predict drug solubility and partitioning in triglyceride solvents from the chemical structures of the solute and the triglyceride would be highly useful in drug formulation development and in screening drug candidates for lipid solubility and possibly drug bioavailability [15].
• METHODS: Cell death was induced by a variety of apoptotic stimuli in various EGFP-expressing mammalian cell lines, including those routinely used in anti-cancer drug screening [16].

Anatomical context of Drug Evaluation, Preclinical

• Identification of MDR cell lines used for large-scale in vitro anticancer drug screening will facilitate interpretation of data in a way which may allow identification of new drug leads of potential value in treatment of MDR tumor cell populations [17].
• Electrical kindling via unilateral implanted depth electrodes in rats is currently the most commonly used model for temporal lobe epilepsy, but the use of this model in drug screening for the identification of novel anticonvulsants is markedly hampered by the laborious and time-consuming preparation and the size of the animals [18].
• To develop a drug screening system, we introduced expression vectors carrying the mouse N-methyl-D-aspartate (NMDA) receptor channel epsilon1 and zeta1 subunit cDNAs under the promoter of the Drosophila heat shock protein hsp70 into Chinese hamster ovary (CHO) cells [19].
• Targeted drug screening revealed a compound, Ruthenium Red, which potently blocked proliferation of human T-cells [20].
• The possible bifunctional activity of the Neutral Red assay as a test for cellular viability and estimating the DNA content of hybridoma cells is discussed along with its application in a drug screening programme [21].

Associations of Drug Evaluation, Preclinical with chemical compounds

• Some of the subjects with postdexamethasone cortisol increases reported drug discontinuation in the drug histories they gave at admission, but in three, drug screening provided the only evidence of prior drug use [22].
• Glutathione-associated enzymes in the human cell lines of the National Cancer Institute Drug Screening Program [23].
• This technique has potential applications in drug screening, such as measuring the dose-response curve of isoproterenol, a beta-adrenergic agonist with a positive chronotropic effect [24].
• Univariate analyses of aggregates of urine drug screening showed generally favorable outcomes for baclofen, but not at statistically significant levels [25].
• In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated [26].

Gene context of Drug Evaluation, Preclinical

• Here, we described a novel drug screening system designated to detect compounds that inhibit the function of Pdr5 [27].
• Repression of Nrf2-mediated transcription by E(2)-bound ERalpha expands our knowledge of E(2)-regulated genes and provides a potential drug-screening target for the development of selective estrogen receptor modulators with a lower risk of causing cancer [28].
• These results strongly support the conclusion that recombinant human DBH from Drosophila S2 cells can be used in place of human neuroblastoma-derived DBH for drug screening, characterization of the enzyme's physicochemical properties, and determination of structure-function relationships [29].
• An amperometric biosensor with human CYP3A4 as a novel drug screening tool [30].
• Interlocking MELK with the drug screening machinery provides new clues related to the selection of target proteins, and functionally relevant hits and drug leads [31].

Analytical, diagnostic and therapeutic context of Drug Evaluation, Preclinical

• During a 6-month monitoring period, carisoprodol was detected in the urine specimens of 19 patients for whom drug screening had been ordered for purposes of patient care [32].
• 4. In conclusion, monitoring of R123 transport in living cells by confocal microscopy in addition to fluorimetric assay is a sensitive tool to study P-gp affinity in drug screening that is especially useful for early phases of drug development [33].
• While N-phosphonacetyl-L-aspartic acid (PALA), an inhibitor of de novo pyrimidine biosynthesis, demonstrated a unique spectrum of activity during preclinical drug evaluation, multiple clinical trials have shown it to possess minimal clinical activity [34].
• We investigated whether the results of routine urine drug screening for cocaine would be positive after dacryocystorhinostomy [35].
• During an 18-month drug-screening period, 34 specimens tested positive for amphetamines with the Roche Abuscreen Radioimmunoassay for Methamphetamine (High Specificity); based on gas chromatographic-mass spectrometric (GC-MS) analysis, the presence of 3,4-methylenedioxymethamphetamine (MDMA) was suspected [36].

References