• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.493-509
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• 2015

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.

• 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.

• Journal of the Korean Magnetic Resonance Society
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• v.9 no.1
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• pp.29-37
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• 2005

Intra-cellular drug uptake in Xenopus laevis oocyte has been elucidated using localized MR spectroscopy (MRS) and PFG NMR techniques at a 600 $MH_z$(Bruker, 14.1 T) NMR spectrometer. The localized MRS has been done with a homemade probe, and shows the intra-cellular uptake of nicotinamide. The self-diffusion of the molecule in Xenopus oocyte was obtained by PFG NMR technique. The measured data are well fitted with a linear combination of two exponential functions, which shows that there are two types of drug molecules, intra-and extra-cellular molecules. Diffusion coefficients of intra- and extra-cellular drug molecules are 3.7 $\times$ $10^{-11}$ $\m^{2}/s$and 6.4 $\times$ $10^{-10}$ $\m^{2}/s$, respectively. In the weighting factors there is shown that about 5% of drug molecule is inside the cells. These techniques can be used for drug screening in molecule-, cell-, and tissue-based preclinical test.

• Archives of Pharmacal Research
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• v.4 no.2
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• pp.99-107
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• 1981

To investigate the protein binding characteristics of ibuprofenlysine, the effects of drub conentration, pH, ionic strength and protein concentration on the binding of drug to protein concentration on the binding of drug to protein were studied by fluorescence probe method. The conformational change of protein was investigated by circular dichroism (CD) measurement. As the concentration of drug increases, the association constant decreases. These may be due to complex formation of the probe and drug, or the interaction of the protein-probe complex and drug. The association constant for ibuprofenlysine increased with increasing protein concentration. These finding suggest a sharing of one ibuprofenlysine molecule by more than one protein molecule in the binding. The binding between ibuprofenlysine and protein was dependent on pH and ionic strength. It seems that both hydrophobic binding and some electrostatic forces are involved in the binding of ibuprofenlysing to protein.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.94-95
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• 2002

Drug targeting to the central nervous system (CNS) is the limiting factor in CNS drug development because most of drug do not cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB) in vivo. One strategy for drug targeting to the brain is to use endogenous BBB transport systems. (omitted)

• Macromolecular Research
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• v.11 no.4
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• pp.207-223
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• 2003

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

• 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)

• Corrosion Science and Technology
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• v.21 no.1
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• pp.21-31
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• 2022

Potentiodynamic polarization, EIS measurements, quantum chemical calculations, and molecular dynamic simulations were used to investigate the corrosion behavior of mild steel in 0.5 M aqueous hydrochloric acid medium in the presence or absence of nystatin drug. Potentiodynamic tests suggested that this molecule could act as a mixed inhibitor due to its adsorption on the mild steel surface. The objective of this study was to exploit theoretical calculations to gain a better understanding mechanism of inhibition. Calculating the adsorption behavior of the investigated molecule on Fe (1 1 0) surface was accomplished using Monte Carlo simulation. Molecules were also investigated using Density Functional Theory (DFT), specifically PBE functional, in order to identify the link between molecular structure and corrosion inhibition behavior of the compound under investigation. Adsorption energies between nystatin and iron were estimated more accurately by utilizing Molecular Mechanics calculation with Periodic Boundary Conditions (PBC). Estimated theoretical parameters significantly assisted our understanding of the corrosion inhibition mechanism exhibited by this molecule. They were found to be in accord with experimental results.

• Archives of Pharmacal Research
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• v.12 no.3
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• pp.160-165
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• 1989

Binding of sulfaethidole to bovine serum albumin was studied by equilibrium dialysis, fluorescence probe technique, uv difference spectrophotometry and circular dichroism. Equilibrium dialysis method enabled us to estimate the total number of drug binding sites of albumin molecule. For sulfaethidole, albumin had 6 primary and 40 secondary binding sites. The primary and secondary binding constants were 0.9 * 10/sup 5/ M/sup -1/ and 0.2 * 10/sup 6/ M/sup -1/, respectivitely. 1-Anilino-8-naphthalenesulfonate (ANS) and 2-(4-hydroxylbenzeneazo)- benzoic acid (HBAB) were used as the fluorescence probe and the uv spectrophotometric probe, respectively. In fluorescence probe technique, results indicated that the number of higher affinity drug binding site of albumin was 1 and the number of lower affinity drug binding sites of albumin was 3, and the primary and secondary drug binding constants for bovine serum albumin were 2.15 * 10/sup 5/M/sup -1/ and 1.04 * 10/sup 5/ M/sup -1/, respectively. In uv difference spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above results suggest that several different methods should be used in ompensation for insufficient information about drug binding to albumin molecule given by only one method.

• The Korean Journal of Applied Statistics
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• v.24 no.3
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• pp.495-503
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• 2011

When a patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency(EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.