• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2291-2295
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• 2016

Small molecule tyrosine kinase inhibitors targeting HER 2 receptors have emerged as an important therapeutic approach in inhibition of downstream proliferation and survival signals for the treatment of breast cancers. Recent drug discovery efforts have demonstrated that naturally occurring polyphenolic compounds like delphinidin have potential to inhibit proliferation and promote apoptosis of breast cancer cells by targeting HER2 receptors. While delphinidin may thus reduce tumour size, it is associated with serious side effects like dysphonia. Owing to the narrow therapeutic window of delphinidin, the present study aimed to identify high affinity compounds targeting HER2 with safer pharmacological profiles than delphinidin through virtual screening approaches. Delphinidin served as the query parent for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. The compounds retrieved were further subjected to Lipinski and Verber's filters to obtain drug like agents, then further filtered by diversity based screens with a cut off of 0.6. The compound with Pubchem ID: 91596862 was identified to have higher affinity than its parent. In addition it also proved to be non-toxic with a better ADMET profile and higher kinase activity. The compound identified in the study can be put to further in vitro drug testing to complement the present study.

• 대한방사성의약품학회지
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• 제7권1호
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• pp.33-40
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• 2021

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

• Genomics & Informatics
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• 제12권2호
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• pp.64-70
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• 2014

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8155-8159
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• 2014

Background: Breast cancer is the serious health concern in India causing the highest mortality rate in females, which occurs due to uncontrolled cell division and can be metastasize to other parts of the human body. Interactions with estrogen receptor (ER) alpha are mainly responsible for the malignant tumors with regulation of the transcription of various genes as a transcription factor. Most of the drugs currently used for the breast cancer treatment produce various side effects and hence we focused on natural compounds which do not exhibit any toxic effect against normal human cells. Materials and Methods: Structure of human ER was retrieved from the Protein Data Bank and the structures of flavonoid compounds have been collected from PubChem database. Molecular docking and drug likeness studies were performed for those natural compounds to evaluate and analyze the anti-breast cancer activity. Results: Finally two compounds satisfying the Lipinski's rule of five were reported. The two compounds also exhibited highest binding affinity with human ER greater than 10.5 Kcal/mol. Conclusions: The results of this study can be implemented in the drug designing pipeline.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.83-95
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• 2010

Over the years, nanoparticle drug delivery systems have demonstrated versatile potentials in biological, medical and pharmaceutical applications. In the pharmaceutical industry nanotechnology research has mainly focused on providing controlled drug release, targeting their delivery to specific organs, and developing parenteral formulations for poorly water soluble drugs to improve their bioavailability. Achievement in polymer industry has generated numerous polymers applicable to designing nanoparticles. From viewpoints of product development, a nanocarrier material should meet requirements for biodegradability, biocompatibility, availability, and regulatory approval crieteria. Albumin is indeed a material that fulfills such requirements. Also, the commercialization of a first albumin-bound paclitaxel nanoparticle product (Abraxane$^{TM}$) has sparked renewed interests in the application of albumin in the development of nanoparticle formulations. This paper reviews the intrinsic properties of albumin, its suitability as a nanocarrier material, and albumin-based parenteral formulation approaches. Particularly discussed in detail are albumin-based particulate injectables such as Abraxane$^{TM}$. Information on key roles of albumin in the nab$^{TM}$ technology and representative manufacturing processes of albumin particulate products are provided. It is likely that albumin-based particulate technology would extend its applications in delivering drugs, polypeptides, proteins, vaccines, nucleic acids, and genes.

• 한국연소학회지
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• 제11권4호
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• pp.9-13
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• 2006

Recent advances in energetic materials modeling and high-resolution hydrocode simulation enable enhanced computational analysis of bio-medical treatments that utilize high-pressure shock waves. Of particular interest is in designing devices that use such technology in medical treatments. For example, the generated micro shock waves with peak pressure on orders of 10 GPa can be used for treatments such as kidney stone removal, transdermal micro-particle delivery, and cancer cell removal. In this work, we present a new computational methodology for applying the high explosive dynamics to bio-medical treatments by making use of high pressure shock physics and multi-material wave interactions. The preliminary calculations conducted by the in-house code, GIBBS2D, captures various features that are observed from the actual experiments under the similar test conditions. We expect to gain novel insights in applying explosive shock wave physics to the bio-medical science involving drug injection. Our forthcoming papers will illustrate the quantitative comparison of the modeled results against the experimental data.

• 통합자연과학논문집
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• 제9권4호
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• pp.268-274
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• 2016

Filariasis causing nematode Brugia malayi is shown to harbor wolbachia bacteria as symbionts. The sequenced genome of the wolbachia endosymbiont from B.malayi (wBm) offers an unprecedented opportunity to identify new wolbachia drug targets. Hence the enzyme carbonic anhydrase from wolbachia endosymbiont of Brugia malayi (wBm) which is responsible for the reversible interconversion of carbon dioxide and water to bicarbonate and protons (or vice versa) is chosen as the drug target for filariasis. This enzyme is thought to play critical functions in bacteria by involving in various steps of their life cycle which are important for survival, The 3D structure of wBm carbonic anhydrase is predicted by selecting a suitable template using the similarity search tool, BLAST. The BLAST results shows a hexapeptide transferase family protein from Anaplasma phagocytophilum (PDB ID: 3IXC) having 77% similarity and 54% identity with wBm carbonic anhydrase. Hence the above enzyme is chosen as the template and the 3D structure of carbonic anhydrase is predicted by the tool Modeller9v7. Since the three dimensional structure of carbonic anhydrase from wolbachia endosymbiont of Brugia malayi has not yet solved, attempts were made to predict this protein. The predicted structure is validated and also molecular docking studies are carried out with the suitable inhibitors that have been solved experimentally.

• 한국연소학회:학술대회논문집
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• 한국연소학회 2006년도 제32회 KOSCO SYMPOSIUM 논문집
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• pp.213-217
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• 2006

Recent advances in energetic materials modeling and high-resolution hydrocode simulation enable enhanced computational analysis of bio-medical treatments that utilize high-pressure shock waves. Of particular interest is in designing devices that use such technology in medical treatments. For example, the generated micro shock waves with peak pressure on orders of 10 GPa can be used for treatments such as kidney stone removal, trans-dermal micro-particle delivery. and cancer cell removal. In this work, we present a new computational methodology for applying the high explosive dynamics to bio-medical treatments by making use of high pressure shock physics and multi-material wave interactions. The preliminary calculations conducted by the in-house code, GIBBS2D, captures various features that are observed from the actual experiments under the similar test conditions. We expect to gain novel insights in applying explosive shock wave physics to the bio-medical science involving drug injection. Our forthcoming papers will illustrate the quantitative comparison of the modeled results against the experimental data.

• Journal of Veterinary Science
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• 제22권3호
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• pp.25.1-25.16
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• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.

• Korean Chemical Engineering Research
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• 제58권4호
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• pp.541-549
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• 2020

약물 전달 시스템(Drug Delivery System, DDS)은 인체에 발생한 질환을 치료를 할 때 약물을 효과적으로 투약하므로써 약물성분에 의한 부작용을 최소화하고, 약물의 효능을 최대한으로 크게하기 위해 기존의 알려진 성분의 약물이나 새로운 성분의 제형을 설계하여 환자의 약물치료 과정을 최적화하는 목적을 지향하는 기술로 정의된다. 본 연구에서는 Tripolyphosphate (TPP)의 농도가 키토산과의 가교결합을 통하여 제조되는 Chitosan nanoparticles (CNPs)의 크기에 미치는 영향을 측정하여 TPP의 농도가 낮을수록 작은 크기의 입자가 형성되는 것을 확인하였다. 그리고 산화철(Fe₃O₄)의 양에 따른 CNPs-Fe₃O₄의 특성을 측정하여 Fe₃O₄의 양이 많을수록 자성 약물 전달체로써의 특성이 잘 나타남을 확인하였다. 닌히드린 반응(Ninhydrin test)를 통하여 저농도 구간(0.004~0.02 wt%)에서는 Y = 0.00373 exp(179.729X) - 0.0114 (R² = 0.989), 고농도구간(0.02~0.1wt%)에서는 Y = 21.680X - 0.290 (R² = 0.999)의 γ-aminobutyric acid (GABA)의 농도에 따른 검량선을 얻었다. 이 검량선을 사용하여 흡수를 위하여 넣어주는 GABA의 양에 따른 최대 흡수율의 관계식 Y = -136.527 exp [(-90.0862)X] + 64.724 (R² = 0.997) 을 얻었으며, 초기에 넣어주는 GABA의 양이 약 0.04 g인 지점부터는 약 62.5%로 흡수율이 일정해 지고, 시간에 따른 GABA-Fe₃O₄-CNPs로부터 방출되는 GABA의 양을 측정하여 약 24 hr 이후부터 약물 방출이 종료되는 것을 확인하였다. 또한 최적의 조건에서 만들어진 GABA-Fe₃O₄-CNPs는 약 150 nm의 구형 입자이며, 그에 따른 입자의 특성이 잘 나타나는 것을 확인하여 약물 전달체로써 적합함을 알 수 있었다.