• Toxicological Research
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• v.29 no.1
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• pp.1-6
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• 2013

The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

• Journal of Korean Institute of Industrial Engineers
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• v.39 no.5
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• pp.403-411
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• 2013

The quality of the products/processes has been improved remarkably since robust design (RD) methodology is applied into the practice manufacturing processes. A model building method based on the dual responses methods for multiple and time oriented responses on a drug development process is employed in this paper instead of the previous methods that handle the static nature of data and single response. Subsequently, the optimal solutions of a multiple and time series RD problem are obtained by using the proposed augmented weighted Tchebycheff method that has a significant flexibility on assigning weights. Finally, a pharmaceutical case study associated with a generic drug development process is conducted in order to illustrate the efficient optimal solutions from the proposed model.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.151-159
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• 2008

Consultation program for pharmaceutical development is a new system in which pharmaceutical companies meet and discuss scientific and/or regulatory issues with drug regulatory authority in the research process and before submitting new drug applications. This program helps pharmaceutical companies reduce uncertainties in the research and development and increase the possibilities of getting drug marketing approval. Developed countries such as US, EU, and Japan have implemented various forms of pre-submission meetings or consultation programs since the mid-1990s. The rapid development of technology in pharmaceutical R&D increases the importance of communication between drug development companies and drug regulatory authority in Korea, too. In designing the consultation program, it is desirable to focus on the stages of clinical trials which take the longest period of time and the biggest amount of money in the pharmaceutical R&D process. We suggested that results or recommendations by drug regulatory authorities in pre-submission meetings or consultations be formally documented and considered in review process. Explicit scientific reasons are required for changing the results from consultations.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.222-229
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• 2020

The process of drug discovery and drug development consumes billions of dollars to bring a new drug to the market. Drug development is time consuming and sometimes, the failure rates are high. Thus, the pharmaceutical industry is looking for a better option for new drug discovery. Drug repositioning is a good alternative technology that has demonstrated many advantages over de novo drug development, the most important one being shorter drug development timelines. In the last two decades, drug repositioning has made tremendous impact on drug development technologies. In this review, we focus on the recent advances in drug repositioning technologies and discuss the repositioned drugs used for inflammatory diseases such as sepsis, asthma, and atopic dermatitis.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.267-274
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• 2014

Drug development and preclinical trials are challenging processes and more than 80% to 90% of drug candidates fail to gain approval from the United States Food and Drug Administration. Predictive and efficient tools are required to discover high quality targets and increase the probability of success in the process of new drug development. One such solution to the challenges faced in the development of new drugs and combination therapies is the use of low-cost and experimentally manageable in vivo animal models. Since the 1980's, scientists have been able to genetically modify the mouse genome by removing or replacing a specific gene, which has improved the identification and validation of target genes of interest. Now genetically engineered mouse models (GEMMs) are widely used and have proved to be a powerful tool in drug discovery processes. This review particularly covers recent fascinating technologies for drug discovery and preclinical trials, targeted transgenesis and RNAi mouse, including application and combination of inducible system. Improvements in technologies and the development of new GEMMs are expected to guide future applications of these models to drug discovery and preclinical trials.

• Korean Journal of Clinical Pharmacy
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• v.18 no.2
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• pp.84-96
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• 2008

In the recent, pharmacokinetic (PK)/pharmacodynamic (PD) modeling has appeared as a critical path tools in new drug development to optimize drug efficacy and safety. PK/PD modeling is the mathematical approaches of the relationships between PK and PD. This approach in new drug development can be estimated inaccessible PK and PD parameters, evaluated competing hypothesis, and predicted the response under new conditions. Additionally, PK/PD modeling provides the information about systemic conditions for understanding the pharmacology and biology. These advantages of PK/PD model development are to provide the early decision-making information in new drug development process, and to improve the prediction power for the success of clinical trials. The purpose of this review article is to summarize the PK/PD modeling process, and to provide the theoretical and practical information about widely used PK/PD models. This review also provides model schemes and the differential equations for the development of PK/PD model.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.9-17
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• 2010

Polymorphism has been recognized to be a critical issue throughout the drug product development process. Most of solid phase drugs have polymorphism, which has generated a great deal of interest and the field has been evolving rapidly. Preferably, thermodynamically most stable form of a drug substance is selected to obtain consistent bioavailability over its shelf life and various storage conditions. Moreover, it has the lowest potential for conversion from one polymorphic form to another. However, metastable or amorphous forms may be used intentionally to induce faster dissolution rate for rapid drug absorption and higher efficacy. For pharmaceutical industry, polymorphism is one of the key activities in form selection process together with salt selection. This article introduces the main features in the investigation of solid form selection especially polymorphic behavior with thermodynamic backgrounds, physicochemical properties with solubility, dissolution, and mechanical properties, and characterization techniques for proper analysis. The final form can be recommended based on the physicochemical and biopharmaceutical properties and by the processability, scalability and safety considerations. Pharmaceutical scientists especially in charge of formulation need to be well aware of the above issues to assure product quality.

• Genomics & Informatics
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• v.19 no.4
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.84-85
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• 2003

The process of drug development has seen major changes over the last two decades with the movement away from standard small molecule drug discovery programs, through computer-assisted drug design methodologies towards biotechnologically derived products. The aim of duplication of endogenously active materials to be administered exogenously has enormous impact on development practices and evaluation of safety.(omitted)

• Proceedings of the Membrane Society of Korea Conference
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• 1996.10a
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• pp.18-21
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• 1996

Virus and DNA removal in bio-drug manufacturing processes has received a great deal of attention in recent years. Removing of a virus using a membrane process is a promising method, because inactivated virus can be removed from the bio-drug and the process can be used as an additional and security inactivation after the method of general heat-inactivation of the virus in the bio-drug. The FDA and the biopharmaceutical industry have recently announced strict guidelines for impurities of virus and DNA contamination. The regulatory guidelines on residual amounts of DNA in mammalian cell culture products require DNA contamination of less than 100 pg/dose. Therefore, permeation and rejection of DNA through the porous membranes have become important in the application of DNA removal in bio-drug manufacturing using membrane technology. In this study, the permeation of DNA and chromatin through regenerated cellulose hollow fibers that have a mean pore diameter of 15 nm was investigated.