• Title/Summary/Keyword: drug design

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An Analysis of the Existing Guidelines and Clinical Trials for the Development of the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) (위식도역류질환 한약제제 임상시험 가이드라인 개발을 위한 관련 국내 가이드라인 분석 및 기존 한약임상시험과의 비교)

  • Han, Ga-jin;Leem, Jung-tae;Kim, Jin-sung;Lee, Jun-hee
    • The Journal of Internal Korean Medicine
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    • v.37 no.1
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    • pp.90-108
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    • 2016
  • Objectives: This study aimed to learn what should be considered in the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) by analyzing the existing guidelines and clinical trials.Methods: The development committee searched the existing guidelines for herbal medicinal products or GERD. Then, clinical trials related to GERD using herbal medicine were selected. The chosen trials were analyzed in terms of their inclusion and exclusion of participants, intervention, comparators, outcome, and trial design. Then, we compared the results of the analysis according to the regulations and guidelines of the Ministry of Food and Drug Safety to suggest the issues that we will have to consider when developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).Results: As a result, few guidelines for GERD and clinical trials with herbal medicinal products were located in the national institution homepage. In addition, 8 articles were found using the following combination of search terms: “Gastroesophageal reflux disease”, “GERD”, “herbal medicine”, “herbal therapy”, “Korean Medicine”, “Traditional Chinese Medicine”, and “TCM”. Even though all trials had their own unique research questions, all studies were performed using a randomization method. Most trials included participants with reflux esophagitis, but two trials targeted proton pump inhibitor-refractory GERD. The type of intervention varied, such as decoction, granules, and capsules. Additionally, individualized herbal medicines were used in two studies. Comparators were diverse, such as placebo, Western medicine, and electro-acupuncture. The most frequently used outcome for efficacy was the effectiveness rate. In addition, the outcome for evaluating quality of life, esophageal mucosa and pressure, esophageal acid reflux, and recurrence rates were used. Safety was investigated by recording adverse events and carrying out laboratory tests.Conclusions: We identified some issues by reviewing the existing guidelines and comparing them with clinical trials for GERD and herbal medicinal products. These results will be utilized for developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).

The Structural and Functional Role of p53 as a Cancer Therapeutic Target (암 치료 표적으로서 p53의 구조적 및 기능적 역할)

  • Han, Chang Woo;Park, So Young;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.28 no.4
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    • pp.488-495
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    • 2018
  • The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

The Effect of Magnolol on UVB-induced Inflammation Damage Control via the Nrf2-SOCS3-Jak2-STAT3 Pathway in Human Dermal Fibroblasts (마그놀롤의 HDF세포에서 Nrf2-SOCS3-Jak2-STAT3에 의한 UVB 유래 염증데미지 조절)

  • Nam, Young sun;Ji, Juree
    • Journal of Life Science
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    • v.30 no.10
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    • pp.867-876
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    • 2020
  • This study investigated the repair of UVB-induced cell damage by magnolol. We performed a drug-repurposing screen, and, in the STAT3 reporter gene assay, magnolol was identified as a suppressor of STAT3 that improves the cell viability of HDF cells. HDF cells treated with IL-6, UVB, and IFNγ showed the highest expression of Jak2 and phosphorylated STAT3 (p-STAT3), and magnolol was able to decrease the expression of Jak2 and p-STAT3 in UVB-induced cells. Moreover, UVB-damaged cell growth increased significantly in correlation with both reactivation and with magnolol in a dose-dependent manner. Compared with AG490 (a Jak2 inhibitor) treatment of UVB-treated HDF cells, cell proliferation increased significantly. We confirmed that AG490 and magnolol reduced TNF-α concentrations, and Western blotting (protein level) showed decreases in Jak2 and p-STAT3 expression in only the magnolol-treated cells. The expression of Jak2, p-STAT3, and SOCS3 also increased only after treatment with magnolol. Cells were treated with magnolol and ML385 (an NRF2 inhibitor), and these secondary metabolites reduced cell proliferation and NRF2 expression. The amount of MMP9 was also increased by cotreatment with magnolol and ML385. Collectively, these results demonstrate the potential of magnolol for repairing cells after UVB-induced damage by regulating the expression of NRF2, SOCS3, Jak2, and STAT3.

흑염소의 체내수정란 생산에 관한 연구

  • 최창용;조숙현;한만희;권응기;최성복;최연호;최순호;손동수;최상용
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.86-86
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    • 2002
  • 면양과 염소가 최근 수십년동안 세계여러 나라에서 번식생리의 연구를 위한 모델로 사용되어 왔는데, 체내수정란의 생산에 관한 영역도 유럽을 중심으로 활발하게 연구되어왔다. 수정란생산을 위한 발정동기화방법, 과배란처리 및 수정란회수방법 기술은 현재 상당히 많은 기술진척이 이루어진 상태이나, 우리나라 고유의 재래유전자원인 흑염소에는 이를 위한 기술이 미진한 실정이므로 본 실험에서는 흑염소의 체내수정란생산기술을 확립하여 재래가축 유전자원보존을 위한 기초기술을 마련하고자 한다. 축산기술연구소 남원지소에서 사육하고 있는 체중 20kg 이상의 건강한 흑염소를 이용하여 발정동기화를 위해 controlled intravaginal drug release(CIDR)를 질내에 14일 동안 삽입하고, 과배란처리는 FSH를 CIDR 삽입 12, 13, 14일째에 12시간 간격으로 점감법으로 총20mg을 투여하였으며, PGF$_2$a를 13일째 FSH와 함께 투여하였다. CIDR는 14일째의 아침에 제거하였다. 수컷과의 교미는 CIDR제거 24시간후에 GnRH를 투여와 동시에 실시하였으며, 채란은 교미후 3일째에 외과적인 방법으로 실시하였다. CIDR처리경과에 따른 progesterone농도는 CIDR 주입시 바로 수치가 상승하여 제거전까지 6~12ng/m1의 농도를 유지하였으며, 제거즉시 2ng/ml 이하로 떨어졌다. 채란시 평균 배란점은 16.5개, 미배란난포 9.8개였으며, 회수수정란은 6.0개를 나타내어 채란율은 36.4%를 나타내었다. 회수된 수정란의 발달단계는 4-cell 78.9%, 2-cell 5.3%, fragmentation 15.8%를 나타내었다. 이와 같은 체내수정란생산방법을 기반으로 하여 이후 수정란의 동결 및 수정란이식기법에 관한 연구를 수행한다면 우리나라의 재래가축인 흑염소의 유전자원 장기보존과 생산성향상에 기여할 것으로 사료된다.배양액에 30 embryos/50ul 소적으로하여 38.8$^{\circ}C$, 5% $CO_2$의 탄산가스 배양기에서 각각 7일간 배양을 실시하였다. 조사된 결과는 SAS/STAT를 이용하여 통계분석을 실시하였다. 체외수정 12시간 후에 난자 급속 염색법으로 염색을 실시한 결과, 모든 처리구에서 핵성숙률(76.4~95.2%), 정자침투율(51.1~66.9%), 웅성전핵형성률(95.2~100%), 다정자침입률(18.2~25.6%) 및 평균침입정자수(1.2~l.4개)에서 유의적인 차이가 인정되지 않았다. 체외배양 48시간 난할률을 조사한 결과, 처리구별 차이(53.9~67.9%)는 인정되지 않았으나, 배양 7일째 배반포형성률은 각각 14.5, 25.4, 17.3 및 12.4%로서 25uM의 $\beta$-ME처리구가 유의적(P<0.05)으로 높은 배발달률을 나타내었고, 총세포수에 있어서는 대조구와 처리구간 유의적인 차이가 인정되지 않았다. 따라서 돼지 난포란을 성숙배양할 때, 25uM $\beta$-ME를 첨가배양하는 것이 양질의 돼지체외수정란을 생산하는 하나의 방법으로 조사되었다.다.natural objects and was popular at the time of Yukjo Dynasty, and there are some documents of that period left both in Japan and Korea. "Hyojedo" in Korea is supposed to have been influenced by the letter design. Asite- is also considered to have been "Japanese Letter Jobcheso." Therefore, the purpose of this study is to look into the origin

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Effectiveness of Hand Massage Combined with Analgesics on Pain Control in Patients with Terminal Cancer (진통제와 병용한 손 마사지가 말기 암환자의 암성통증 조절에 미치는 효과)

  • Lee, Yunmi;Yoon, Hosoon;Lee, Sungwoon;Kim, Young Mi
    • Journal of Hospice and Palliative Care
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    • v.19 no.4
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    • pp.296-302
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    • 2016
  • Purpose: This study examined the effectiveness of a hand massage combined with analgesics on pain control in hospice patients with terminal cancer. Methods: This study is a quasi-experimental study with a single group time series design. The study included 25 terminal cancer patients who were admitted to a hospice ward. Each patient's pain level was measured after analgesics use only (control group). When patients complained of pain again, the pain level was assessed after administering a combination of hand massage and analgesics (experimental group). As for the experimental treatment, the participants were provided with oil hand massage on each hand for 5 minutes. Results: The experimental group and the control group showed no significant differences in the changes of pain score (F=0.74, P=0.3939). Conclusion: Although the pain level of the experimental group did not significantly improve compared with the control group, their pain levels tended to be low to begin with. Thus, a complementary utility value of hand massage cannot be completely excluded in terminal cancer patients. Since the pain level significantly changed according to the dosage of analgesic, nurses need more education and research on analgesic drug therapy for terminal cancer patients.

Design and Implementation of MPEG-21 Testbed (MPEG-21 Testbed의 설계 및 구현)

  • 손정화;권혁민;손현식;조영란;김만배
    • Proceedings of the Korean Society of Broadcast Engineers Conference
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    • 2002.11a
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    • pp.139-143
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    • 2002
  • 1990 년대 후반부터 다양한 디지털 통신망을 이용하여 멀티미디어 컨텐츠 서비스가 가능하게 되었다. 하지만, 멀티미디어 컨텐츠의 전달 및 이용을 위한 기반 구조들의 독자적 발전 및 다양한 통합적 관리 체계 시스템으로 인해, 멀티미디어 컨텐츠 표현 방식의 호환성 문제, 혼재하는 네트워크 전달 방식과 단말 방식의 호환성 문제 등의 잠재적인 문제점이 발생한다. 이런 문제의 대안으로 현재 존재하는 기술 및 기반 구조들 사이의 연동을 통한 큰 프레임워크인 MPEG-21이 진행 중이다. MPEG-21 의 목표는 표준화 목표를 구체화하는 것부터 진행하여, 최종적으로 “다양한 네트워크 환경과 단말기에 있어서, 투명하고 통합적으로 멀티미디어 자원의 이용을 가능하게 하는 것”이다. 본 논문에서는 현재 표준화 작업이 진행 중인 MPEG-21 을 기반으로 하는 Testbed를 제안한다. Testbed는 server, client, DIA(Digital Item Adaptation) 의 세 모듈로 구성된다. Server 의 역할은 멀티미디어 컨텐츠를 Digital Item(DI)으로 생성하고, client 가 DI를 요구할 경우 DIA 모듈을 통해서 변환된 DI를 client 에게 제공한다. DIA 모듈은 server 에서 동작되며 client로부터 요청된 DI를 분석하고 client로부터 전송된 환경 정보를 이용하여 client 환경에 적합하게 변환된 (adapted) DI를 생성하는 것이 주 기능이다. Client 는 server 에 저장되어 있는 DI를 선택하고 user preference, terminal capability 등의 필요한 정보를 server로 전송한다. Testbed 에서는 스포츠 경기의 동영상, 정지 영상, 경기 내용 역사를 기록한 파일 등의 DI를 이용한다. 표현 언어는 XML이며, HTTP 기반의 Web 환경에서 구동되도록 설계된다.스템 사이에 의미 있는 데이터 전송, 지식 획득을 위해 정보 기술 분야에서 활용해야 할 영역으로 XML Web Services, Multi-agent Systems, 전문가 컴뮤니티를 위한 그룹웨어 연구 개발에 관해 사례 중심으로 발표한다.다 신선한 공기를 넣어 주었을 때는 배의 발달이 많이 늦어져 배양 3주째에 다른 처리보다 배의 수가 훨씬 적었다. 체세포배가 발달하는 동안에는 산소를 많이 요구하지 않으나 성숙하는 동안에는 산소를 많이 요구하는 것으로 생각된다.적인 것으로 나타났다. 다만, 곡선형은 물론 직선형에서도 열교환 튜브의 배치밀도, 튜브 길이 및 두께 등의 변화에 따른 최적화 연구가 수반되어야 할 것으로 판단된다.에서 제공된 API는 객체기반 제작/편집 도구에 응용되어 다양한 멀티미디어 컨텐츠 제작에 사용되었다.x factorization (NMF), generative topographic mapping (GTM)의 구조와 학습 및 추론알고리즘을소개하고 이를 DNA칩 데이터 분석 평가 대회인 CAMDA-2000과 CAMDA-2001에서 사용된cancer diagnosis 문제와 gene-drug dependency analysis 문제에 적용한 결과를 살펴본다.0$\mu$M이 적당하며, 초기배발달을 유기할 때의 효과적인 cysteamine의 농도는 25~50$\mu$M인 것으로 판단된다.N)A(N)/N을 제시하였다(A(N)=N에 대한 A값). 위의 실험식을 사용하여 헝가리산 Zempleni 시료(15%$S_{XRD}$)의 기본입자분포로부터 %$S_{XRD}$를 계산한 결과, 16%$S_{XRD}$의 결과값을 얻을 수 있었다. 따라서, 본 연구에서 도출한 관계식들이 유효함을 확인할 수 있었다.계식들이 유효함을 확인할 수 있었다.할 때 약간의 증가

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Effects of locally-delivered minocycline hcl on controlled periodontal disease (Minocycline 국소 약물 방출 제제의 치주질환 치료 효과)

  • Chung, Mi-Hyun;Kwon, Young-Hyuk;Herr, Yeek;Lee, Man-Sup;Park, Joon-Bong
    • Journal of Periodontal and Implant Science
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    • v.28 no.1
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    • pp.37-56
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    • 1998
  • The purpose of this study was to evaluate the clinical and microbiological outcomes following the use of 30% minocycline-loaded polycaprolacton film and 2% minocycline-loaded gel that was applied locally into pockets combined with scaling and root planing. 25 human subjects who were non-pregnant, non-lactating, aged 20-50 and diagnosed as moderate to advanced adult periodontitis were enrolled. Subjects were excluded if they had a history of severe acute or chronic systemic disease, if they required antibiotic prophylaxis for dental treatment for any reason, or if they reported a history suggestive of hypersensitivity reactions to minocycline or tetracycline. 4quadrants that had several teeth with a 5-8mm probing pocket depth and radiographic evidence of alveolar bone loss for each patient were selected and divided into test sites and control sites according to the split-mouth design. Scaling and root planing was done for each site at baseline(0week). Test sites received the minocycline gel and strip and control sites had saline irrigation. The patients received both treatments simyltaneously. Subgingival irrigation of sterile saline was applied to the control sites for approximately 30 seconds. Minocycline strip and gel was applied into the periodontal pocket at 1, 2, 3, 4 weeks each after scaling and root planing in the test sites. The clinical and microbiological measurements were made at baseline and at the follow-up visits 6, 10, 14, 20 weeks. The results of this study were as follows; 1. The sulcular bleeding index, probing pocket depth and Periocheck test was significantly reduced and the relative proportions of spirochetes and motile rods were significantly reduced and the proportion of cocci was correspondingly increased, in locally delivered minocycline strip group compared to saline irrigation group. 2. In locally delivered minocycline gel group, The effect was the same with minocycline strip group as compared with saline irrigation therapy. 3. There was no significant differences between minocycline strip group and minocycline gelgroup. In conclusion, minocycline HCl local drug delivery combined with scaling and root planing may provide added improvement of clinical and microbiological responses by inhibiting bacterial recolonization of treated sites. It is suggested that the local administration of minocycline-HCl in the periodontal pocket is effective when combined with subgingival mechanical debridement.

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Pharmacophore Identification for Peroxisome Proliferator-Activated Receptor Gamma Agonists

  • Sohn, Young-Sik;Lee, Yu-No;Park, Chan-In;Hwang, S-Wan;Kim, Song-Mi;Baek, A-Young;Son, Min-Ky;Suh, Jung-Keun;Kim, Hyong-Ha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.32 no.1
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    • pp.201-207
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    • 2011
  • Peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors and their activation induces regulation of fatty acid storage and glucose metabolism. Therefore, the $PPAR\gamma$ is a major target for the treatment of type 2 diabetes mellitus. In order to generate pharmacophore model, 1080 known agonists database was constructed and a training set was selected. The Hypo7, selected from 10 hypotheses, contains four features: three hydrogen-bond acceptors (HBA) and one general hydrophobic (HY). This pharmacophore model was validated by using 862 test set compounds with a correlation coefficient of 0.903 between actual and estimated activity. Secondly, CatScramble method was used to verify the model. Hence, the validated Hypo7 was utilized for searching new lead compounds over 238,819 and 54,620 chemical structures in NCI and Maybridge database, respectively. Then the leads were selected by screening based on the pharmacophore model, predictive activity, and Lipinski's rules. Candidates were obtained and subsequently the binding affinities to $PPAR\gamma$ were investigated by the molecular docking simulations. Finally the best two compounds were presented and would be useful to treat type 2 diabetes.

Apoptotic Activity of Curcumin and EF-24 in HTB-41 Human Salivary Gland Epidermoid Carcinoma Cells

  • Kim, Ji-Won;Lee, Seul Ah;Go, Dae-San;Park, Byung-Sun;Kim, Su-Gwan;Yu, Sun-Kyoung;Oh, Ji-Su;Kim, Chun Sung;Kim, Jeongsun;Park, Jong-Tae;Kim, Do Kyung
    • International Journal of Oral Biology
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    • v.40 no.2
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    • pp.63-69
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    • 2015
  • Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.

Expression of MEK1 Fusion Protein in Yeast for Developing Cell Based Assay System, a Major Substrate of LeTx (Yeast내에서 MEK1 융합 단백질 발현 및 Lethal Factor 활성 검증)

  • Hwang, Hye-Hyun;Kim, Joung-Mok;Choi, Kyoung-Jae;Park, Hae-Chul;Han, Sung-Hwan;Chung, Hoe-Il;Koo, Bon-Sung;Park, Joon-Shik;Yoon, Moon-Young
    • Korean Journal of Microbiology
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    • v.42 no.3
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    • pp.195-198
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    • 2006
  • Lethal toxin is a critical virulence factor of anthrax. It is composed two protein: protective antigen (PA) and lethal factor (LF). PA binds to specific cell surface receptors and, forms a membrane channel that mediates entry of LF into the cell. LF is a zinc-dependent metalloprotease, which cleaves MKKs [MAPK (mitogen-activated protein kinase) kinases] at peptide bonds very close to their N-termini. In this study, we suggest application of cell-based assays in the early phase of drug discovery, with a particular focus on the use of yeast cells. We constructed MEK1 expression system in yeast to determine LF activity and approached cell-based assay system to screen inhibitors, in which the results covering the construction of LF-substrate in yeast expression vector, expression, and LF-mediated proteolysis of substrate were described. These results could provided the basic steps in design of cell-based assay system with the high efficiency, rapidly and easy way to screening of inhibitors.