• Journal of Integrative Natural Science
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• v.6 no.2
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• pp.100-103
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• 2013

Using computational approaches we can dock small molecules into the structures of Macromolecular targets and then score their potential complementarity to binding sites is widely used in hit identification and lead optimization techniques. This review seeks to provide the application of docking in structure-based drug design (binding mode prediction, Lead Identification and Lead optimization), and also discussed how to manage errors in docking methodology in order to overcome certain limitations of docking and scoring algorithm.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.518-523
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• 2004

An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, Fc$\varepsilon$RI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves of Castanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3',4'-dichlorophenyl group displayed strong inhibitory activities on Fc$\varepsilon$RI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents.

• YAKHAK HOEJI
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• v.59 no.4
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• pp.151-157
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• 2015

The purpose of this study is to demonstrate how lead compounds are best optimized with the application of in silico QSAR and PBPK modeling at the early drug discovery stage. Several predictive QSAR models such as $IC_{50}$ potency model, intrinsic clearance model and brain penetration model were built and applied to a set of virtually synthesized library of the BACE1 inhibitors. Selected candidate compounds were also applied to the PBPK modeling for comparison between the predicted animal pharmacokinetic parameters and the observed ones in vivo. This novel lead optimization strategy using QSAR and PBPK modelings could be helpful to expedite the drug discovery process.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.42-42
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• 2003

Recently, Korean Food and Drug Administration (KFDA) has been attempting to modernize the review processes for generic drug products. Obviously, the modernization effort will lead to harmonize the guidelines in the process to the internationally acceptable level. In general, the Korean version of abbreviated new drug application (ANDA) consisted of similarly to those in developed countries (viz, specifications for bulk drug/preparation, bioequivalence, and stability); However, there exists a significant gap in the sophistication of the guidelines between the Korean version and those in the other countries. (omitted)

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.17-24
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• 2007

Objectives : Licorice has been commonly used as a detoxification agent. We previously reported that licorice and its component, liquiritigenin, exhibits cytoprotective activity against Pb-induced toxicity. The present study was conducted to evaluate the effect of liquiritigenin on the lead-induced cytotoxicity in PC-12 cells. Methods : PC-12 cells were pre-treated with liquiritigenin, and further incubated with lead 100 ${\mu}M$ for $12^{\sim}48$ hours. The viability of PC-12 cells was measured by MTT assay, and the levels of proteins were analysed by western blot. Results : Severe cytotoxicity was induced and nitric oxide (NO) production was augmented by the exposure of lead. Liquiritigenin protected cells from lead-induced cytoxicity and reduced NO production in a dose-dependent manner. The inhibition of NO production was due to the suppression of iNOS protein via the inhibition of $NF-{\kappa}B$ nuclear translocation, determined by western blot analysis. Conclusions : These results suggest that liquiritigenin may exert cytoprotective effect against lead toxicity by inhibiting NO production.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.510-516
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• 2015

In this review, lipid A, from its discovery to recent findings, is presented as a drug target and therapeutic molecule. First, the biosynthetic pathway for lipid A, the Raetz pathway, serves as a good drug target for antibiotic development. Several assay methods used to screen for inhibitors of lipid A synthesis will be presented, and some of the promising lead compounds will be described. Second, utilization of lipid A biosynthetic pathways by various bacterial species can generate modified lipid A molecules with therapeutic value.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3345-3349
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• 2013

Hsp90 shows great promise as a therapeutic target due to its potential to disable multiple signaling pathways simultaneously. In this study, we discovered that a natural product, butein moderately inhibited the growth of drug-resistant cancer cells (A2780cis and H1975), and brought about the degradation of oncogenic Hsp90 client proteins. The study demonstrated that butein would be a therapeutic lead to circumvent drug-resistance in cancer chemotherapy. The structure-based screening, synthesis, and biological evaluation of butein are described herein.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1505-1508
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• 2012

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound ($\mathbf{4}$) was first observed to have moderate inhibitory activity against PTP1B with an $IC_{50}$ value of $13.72{\pm}1.53{\mu}M$. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound ($\mathbf{4}$) as the lead compound. Compound $\mathbf{4l}$ ($IC_{50}=3.12{\pm}0.18{\mu}M$) was 4.4-fold more potent than the lead compound $\mathbf{4}$ ($IC_{50}=13.72{\pm}1.53{\mu}M$), and more potent than the positive control, ursolic acid ($IC_{50}=3.40{\pm}0.21{\mu}M$). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.90-90
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• 2003

I describe here a novel and promising approach to drug discovery that involves the identification and assembly of drug-like fragments to afford lead compounds. This approach is attractive for a number of reasons. First, the productive assembly of two weakly bound fragments, even fragments with independent dissociation constants in the low mM range, can potentially afford ligands with sub-micromolar affinities for their targets. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.41-49
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• 1994

The most common conventional method of discovering a drug involves a massive screening of a large number of compounds in chemical libraries or in the extracts from natural sources such as plants or microbial broths followed by chemical modification of one or more active compounds to improve their properties as a drug. When the three-dimensional structure of the target molecule for which the drug is searched is known the drug discovery process can be significantly simplified, This is especially true when the three-dimensional structure of a complex between the target and a lead compound is known. In this lecture our experience on the structure-based drug design for human CDK2(cyclin-dependent protein kinase 2) will be discussed with special emphasis on the strength and weakness of this approach of drug discovery. The regulation of the activity of CDK2 plays an important role in the cell proliferation of normal and cancer cells.