• 제목/요약/키워드: New drug development

검색결과 674건 처리시간 0.028초

Development of Proteomics and Applications of Proteomics in Toxicology

  • Jung, Woon-Won;Huh, Yoon-Ee;Ryu, Jae-Chun;Lee, Eun-Il;Sul, Dong-Geun
    • Molecular & Cellular Toxicology
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    • 제1권1호
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    • pp.7-12
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    • 2005
  • Proteomics has recently received intense scientific interest after the completion of the Human Genome Project, because this genome-based high technology allows to search new drug targets or diagnostic markers. Many proteome projects including Human plasma proteome projects (HPPP), Human liver proteome projects (HLPP), Human brain proteome projects (HBPP), and Mouse and Rat Proteome Project (MRPP) have been carried out and proteomic analytical techniques have been developed in second dimensional electrophoresis (2-DE) and LC/MS system. This powerful method has been applied in toxicology producing a new term "Toxicoproteomics". In this review, recent proteome projects, proteomic technologies, and toxicoproteomics will be discussed.

The Emergence of Behavioral Testing of Fishes to Measure Toxicological Effects

  • Brooks, Janie S.
    • Toxicological Research
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    • 제25권1호
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    • pp.9-15
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    • 2009
  • Historically, research in toxicology has utilized non-human mammalian species, particularly rats and mice, to study in vivo the effects of toxic exposure on physiology and behavior. However, ethical considerations and the overwhelming increase in the number of chemicals to be screened has led to a shift away from in vivo work. The decline in in vivo experimentation has been accompanied by an increase in alternative methods for detecting and predicting detrimental effects: in vitro experimentation and in silico modeling. Yet, these new methodologies can not replace the need for in vivo work on animal physiology and behavior. The development of new, non-mammalian model systems shows great promise in restoring our ability to use behavioral endpoints in toxicological testing. Of these systems, the zebrafish, Danio rerio, is the model organism for which we are accumulating enough knowledge in vivo, in vitro, and in silico to enable us to develop a comprehensive, high-throughput toxicology screening system.

Synthesis of New 3-Arylisoquinolinamines: Effect on Topoisomerase I Inhibition and Cytotoxicity

  • Cho, Won-Jae;Min, Sun-Young;Le, Thanh-Nguyen;Kim, Tae-Sung
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.180.1-180.1
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    • 2003
  • Eukaryotic DNA topoisomerase I (top I) is an essential enzyme that act to relax supercoiled DNA during the transcription, replication and mitosis. Intracellular levels of top I are elevated in a number of human solid tumors, relative to the respective normal tissues, suggesting that controlling the topI level is important to treat cancer. Top I poisons show their antitumor activities by stabilizing the cleavable ternary complex consisting of top I enzyme, DNA, and drug. Thus, top I is a promising target for the development of new cancer chemotherapeutics against a number of solid tumors. (omitted)

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Review of ginsenosides targeting mitochondrial function to treat multiple disorders: Current status and perspectives

  • Huang, Qingxia;Gao, Song;Zhao, Daqing;Li, Xiangyan
    • Journal of Ginseng Research
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    • 제45권3호
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    • pp.371-379
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    • 2021
  • Mitochondrial dysfunction contributes to the pathogenesis and prognosis of many common disorders, including neurodegeneration, stroke, myocardial infarction, tumor, and metabolic diseases. Ginsenosides, the major bioactive constituents of Panax ginseng (P. ginseng), have been reported to play beneficial roles in the molecular pathophysiology of these diseases by targeting mitochondrial dysfunction. In this review, we first introduce the types of ginsenosides and basic mitochondrial functions. Then, recent findings are summarized on different ginsenosides targeting mitochondria and their key signaling pathways for the treatment of multiple diseases, including neurological disorders, cancer, heart disease, hyperglycemia, and inflammation are summarized. This review may explain the common targets of ginsenosides against multiple diseases and provide new insights into the underlying mechanisms, facilitating research on the clinical application of P. ginseng.

생분해성 고분자의 전기분사를 이용한 약물방출 스텐트용 금속표면 코팅 및 ALA방출 거동 (Metal Surface Coating Using Electrospray of Biodegradable Polymers and $\alpha$-Lipoic Acid Release Behavior for Drug-Eluting Stents)

  • 김동민;이봉수;박철호;박귀덕;손태일;정명호;한동근
    • 폴리머
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    • 제34권2호
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    • pp.178-183
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    • 2010
  • 의료용 금속스텐트는 관상동맥계 심장질환을 앓고 있는 환자에 시술되어 상대적으로 생존율을 높여 준다. 그러나, 재협착 및 후기 혈전증으로 인하여 새로운 스텐트의 개발이 시급하게 되었다. 이러한 문제점을 해결하기 위해서 신생내막 과대증식을 막을 수 있는 것으로 알려진 alpha lipoic acid(ALA)를 생분해성 고분자인 poly(lactide-coglycolide)(PLGA), poly(L-lactide)(PLLA) 및 poly($\varepsilon$-caprolactone)(PCL)과 혼합하여 전기분사 방식으로 스테인레스 스틸 표면 위에 코팅하였다. 코팅된 고분자로부터 약물방출 거동은 고분자의 종류와 농도, 용출속도 및 용매의 종류에 따라서 조사하였다. 약물방출 속도는 유리전이온도($T_g$)가 낮은 PCL에서 가장 빨랐으며 PLGA, PLLA 순서를 보였다. 고분자 표면의 거친정도는 용출속도가 증가함에 따라서 증가하였고, 용매의 비등점의 차이에 의해서 약물방출속도가 변화됨을 알 수 있었다. 이러한 약물방출 거동을 조절함으로써 ALA가 담지된 생분해성 고분자로 코팅된 약물방출 스텐트를 실제 임상적용이 가능할 것으로 기대된다.

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

  • Tang, Yan-Hui;Hu, Min;He, Xiao-Peng;Fahnbulleh, Sando;Li, Cui;Gao, Li-Xin;Sheng, Li;Tang, Yun;Li, Jia;Chen, Guo-Rong
    • Bulletin of the Korean Chemical Society
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    • 제32권3호
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    • pp.1000-1006
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    • 2011
  • The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

The Inhibition of Epileptogenesis During Status Epilepticus by Ginsenosides of Korean Red Ginseng and Ginseng Cell Culture (Dan25)

  • N.E., Chepurnova;Park, Jin-Kyu;O.M., Redkozubova;A.A., Pravdukhina;K.R., Abbasova;E.V., Buzinova;A.A., Mirina;D.A., Chepurnova;A.A., Dubina;U.A., Pirogov;M., De Curtis;L., Uva;S.A., Chepurnov
    • Journal of Ginseng Research
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    • 제31권3호
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    • pp.159-174
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    • 2007
  • Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one's biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides $(Rb_1$ Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

Development of New Drug, Epidermal Growth Factor for Chronic Diabetic Foot Ulcer

  • Yoo, Young-hyo
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2000년도 춘계학술대회
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    • pp.3-5
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    • 2000
  • Of 16 million diabetic patients in the USA, 2.4 millions have experienced diabetic foot ulcer and 67,000 have amputations every year. For treatment of diabetic foot ulcer, Americans spend more than $1 billion each year, including $36,000 per patient for complete treatment and $60,000 for each amputation. Neuropathy and ischemia, two common complications of diabetes mellitus, are the primary underlying risk factors for development of diabetic foot ulcers. Ischemic ulcers develop as a result of low perfusion pressure in the foot with inadequate blood supply, whereas neuropathic ulcers develop from loss of protective sensation. In addition, diabetes also increases the risk of infection by impairing the body's ability to eliminate bacteria. From these circumstances, results are chronic wounds with impaired healing ability.

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의료 인공지능 10대 표준화 동향 및 전망 (Top 10 Key Standardization Trends and Perspectives on Artificial Intelligence in Medicine)

  • 전종홍;이강찬
    • 전자통신동향분석
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    • 제35권2호
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    • pp.1-16
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    • 2020
  • "Artificial Intelligence+" is a key strategic direction that has garnered the attention of several global medical device manufacturers and internet companies. Large hospitals are actively involved in different types of medical AI research and cooperation projects. Medical AI is expected to create numerous opportunities and advancements in areas such as medical imaging, computer aided diagnostics and clinical decision support, new drug development, personal healthcare, pathology analysis, and genetic disease prediction. On the contrary, some studies on the limitations and problems in current conditions such as lack of clinical validation, difficulty in performance comparison, lack of interoperability, adversarial attacks, and computational manipulations are being published. Overall, the medical AI field is in a paradigm shift. Regarding international standardization, the work on the top 10 standardization issues is witnessing rapid progress and the competition for standard development has become fierce.

Biochemical Study of Recombinant PcrA from Staphylococcus aureus for the Development of Screening Assays

  • Dubaele, Sandy;Martin, Christophe;Bohn, Jacqueline;Chene, Patrick
    • BMB Reports
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    • 제40권1호
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    • pp.7-14
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    • 2007
  • Helicases are ubiquitous enzymes, which utilize the energy liberated during nucleotide triphosphate hydrolysis to separate double-stranded nucleic acids into single strands. These enzymes are very attractive targets for the development of new antibacterial compounds. The PcrA DNA helicase from Staphylococcus aureus is a good candidate for drug discovery. This enzyme is unique in the genome of S. aureus and essential for this bacterium. Furthermore, it has recently been published that it is possible to identify inhibitors of DNA helicases such as PcrA. In this report, we study the properties of recombinant PcrA from S. aureus purified from Escherichia coli to develop ATPase and helicase assays to screen for inhibitors.