Natural products used as a chemical library for protein–protein interaction targeted drug discovery

Jin, Xuemei,Lee, Kyungro,Kim, Nam Hee,Kim, Hyun Sil,Yook, Jong In,Choi, Jiwon,No, Kyoung Tai Elsevier 2018 Journal of molecular graphics & modelling Vol.79 No.-

<P><B>Abstract</B></P> <P>Protein–protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an <I>in vitro</I> experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This paper provides <I>in silico</I> drug discovery strategy to identify natural products capable to inhibit the protein–protein interactions. </LI> <LI> The predicted PPI inhibitor-like natural products were validated in an in vitro experiment. </LI> <LI> The XIAP inhibitor LENP0044 could be used as a potent template for further chemical optimization. </LI> <LI> Natural products can be used as potent candidates in the design of a PPI-focused chemical library for drug discovery. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

한의진단명과 진단요건의 표준화 연구 III : 3차년도 연구결과 보고

최선미,양기상,최승훈,박경모,박종현,심범상,김성우,노석선,이인선,정진홍,이진용,김달래,임형호,김윤범,박성식,송태원,김종우,이승기,최윤정,신순식 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the third year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows : - analyzing and differentiating of epidemic febrile disease - analyzing and differentiating in accordance with the Sasang constitution medicine based on four-type recognition - differentiation of disease according to pathological changes of Chong and Ren channels - standards for diagnosis of women's disease - standards for diagnosis of children's disease - standards for diagnosis of motor and sensor disturbance (-muscle. born, joint, etc.) - standards for diagnosis of neuropsychiatric disease - standards for diagnosis of five sense organ disease - standards for diagnosis of external disease The indivisual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name, notion of diagnosis pattern, index of differentiation of symptoms and signs, the main point of diagnosis, analysis of diagnosis pattern, discrimination of diagnosis pattern, prognosis, a way of curing a disease, prescription, herbs in common use, disease appearing the diagnosis pattern, documents. The standards for diagnosis of each disease was arranged by the diagnostic requirements in the following order : another name, notion of disease, the main point of diagnosis, analyzing and differentiating of disease, analysis of disease, discrimination of disease, prognosis, a way of curing and prescription of disease, disease in western medicine appearing the disease in oriental medicine, documents.

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

순산소 순환유동층에서 로내 탈황 및 탈질법 적용에 따른 오염물질 거동특성

최경구(Gyung-Goo Choi),나건수(Geon-Soo Na),신지훈(Ji-Hoon Shin),길상인(Sang-In Keel),이정규(Jung-Kyu Lee),허필우(Pil-Woo Heo),윤진한(Jin-Han Yun) 한국청정기술학회 2018 청정기술 Vol.24 No.3

순산소 연소기술은 화력발전에 적용 가능한 유망한 온실가스 감축 기술로 평가되고 있다. 본 연구는 환경적 관점에서 순환유동층을 활용한 순산소 연소조건에 로 내 탈황 및 탈질법을 적용하여 NO 및 SO₂의 거동을 살펴보는 한편, SO₃, NH₃, 그리고 N2O의 발생 경향도 관측하였다. 이를 위해, 연소로 내 석회석 및 요소수를 투입하였다. 로 내 탈황법은 연소가스 내 SO₂ 농도를 ~403에서 ~41 ppm까지 저감하였다. 또한 SO₃ 형성의 주원료인 SO₂가 저감되면서 연소가스 내 SO₃ 농도도 ~3.9에서~1.4 ppm까지 감소되었다. 그러나 석회석 내 CaCO₃가 NO의 발생을 촉진하는 현상도 관측되었다. 연소가스 내 NO 농도는로 내 탈질법을 적용하여 ~26 - 34 ppm까지 저감되었다. 요소수 투입량 증가에 따라 연소가스 내 NH₃ 농도가 증가하여 최대~1.8 ppm으로 나타났으며, N₂O의 농도도 ~61에서 ~156 ppm까지 증가하였다. N₂O 발생량 증가 현상은 요소수의 열분해 과정에서 생성된 HNCO가 N₂O로 전환되어 나타난다. 본 연구의 결과를 통해 로 내 연소가스 세정법을 적용할 경우 NOx 및 SOx의 저감뿐만 아니라, 다른 오염물질의 발생에 대한 주의가 필요할 것으로 보인다. Oxy-fuel combustion is considered as a promising greenhouse gas reduction technology in power plant. In this study, the behaviors of NO and SO₂ were investigated under the condition that in-furnace deNOx and deSOx methods are applied in oxy-fuel circulating fluidized bed combustion condition. In addition, the generation trends of SO₃, NH₃ and N2O were observed. For the purpose, limestone and urea solution were directly injected into the circulating fluidized bed combustor. The in-furnace deSOx method using limestone could reduce the SO₂ concentration in exhaust gas from ~403 to ~41 ppm. At the same experimental condition, the SO₃ concentration in exhaust gas was also reduced from ~3.9 to ~1.4 ppm. This trend is mainly due to the reduction of SO₂. The SO₂ is the main source of the formation of SO₃. The negative effect of CaCO₃ in limestone, however, was also appeared that it promotes the NO generation. The NO concentration in exhaust gas reduced to ~26 - 34 ppm by appling selective non-catalytic reduction method using urea solution. The NH₃ concentration in exhaust gas was appeared up to ~1.8 ppm during injection of urea solution. At the same time, the N₂O generation also increased with increase of urea solution injection. It seems that the HNCO generated from pyrolysis of urea converted into N₂O in combustion atmosphere. From the results in this study, the generation of other pollutants should be checked as the in-furnace deNOx and deSOx methods are applied.

초등 과학 생명 영역 내용에 대한 학생들의 의문 유형과 해결방법에 관한 연구

임채성,최은아,박정인,이수진 부산교육대학교 과학교육연구소 2004 科學敎育硏究 Vol.29 No.-

In this study, the frequencies and types of questions about LIFE areas of the Science Curriculum of elementary school students were investigated through in-depth interviews with twelve 4th and 5th graders. The results of the research can be summarized as follows: (1) In conjectural question, the proportions of 'object exploration question' and 'object verification question' were high in all of the 4th graders and the students of low achievement level. (2) The numbers of causal questions generated by the 4th graders were much higher than those of the 5th graders. (3) The frequencies of the predictive, methodological, applicative questions were very low both in 4th and 5th grade students. (4) The numbers of conjectural questions were more in all students except the low achievement level of 4th graders at not-yet-taken contents than at already-taken ones. (5) The numbers of causal questions were more in all students except the low and middle achievement levels of 4th graders at not-yet-taken contents than at already-taken ones. (6) The numbers of the predictive, methodological, applicative questions of the 4th graders were more at not-yet-taken contents than at already-taken ones, whereas opposite trend in the 5th graders. (7) The numbers of students' curriculum-related questions were more in all students except the low and middle achievement levels of 4th graders at not-yet-taken contents than at already-taken ones. (8) As ways for solving or seeking answers about questions, the 4th graders suggested methods of consulting experts or teachers (23.9%), internet searching (21.6%), and books or science-related encyclopedia (20.3%), while the 5th graders suggested the internet searching (36.5%), consulting experts or teachers (24.8%), and books or science-related encyclopedia (17.7%). Based an these results, we suggest several ways for improving the question-posing abilities of the students and adequate use of students' questions in the process of science teaching learning.

양성 및 음성 정신분열증 환자의 시각적주의폭에 관한 연구

최정인,이형영,윤진상 大韓神經精神醫學會 1988 신경정신의학 Vol.27 No.5

This study was performed to compare the visual attention span among three groups of 22 negative schizophrenics, 29 positive schizophrenics and 30 normal controls. The narrowing and broadening of attention span were tested by comparing correct recognition responses of peripheral visual stimulus. The results are as follows : 1) There was a significant difference in the total number of correct recognition responses among three groups; In controls, the total number of the correct recognition responses was highest and this was followed by positive schizophrenics(P<0.01). The number of the correct recognition responses was higher in larger stimulus size than in small stimulus size in all three groups(P<0.01). 2) Comparing groups and stimulus size; there was no significant difference in large stimulus size. In small stimulus size, there was significant difference between postivive schizophrenics and controls(P<0.05), between negative schizophrenics and controls(P<0.01), and between negative schizophrenics and positive schizophrenics(P<0.01). 3) Comparing groups and display angle, there was no significant difference in display angle 2˚ among three groups, while there was significant difference in display angle 12˚ between negative schizophrenics and controls(P<0.01), and significant difference in display angle 25˚ between negative schizophrenics and controls and between negative schizophrenics and positive schizophrenics(P<0.01), respectively. In summary, these results suggest that negative schizophrenics, unlike postive schizophrenics and controls, are only able to recognize large peripheral stimulus within a narrow display angle, because of narrowing of attention span.

주의력결핍 과잉행동장애 아동에서 틱 장애 동반 여부에 따른 확산 텐서 영상 비교 연구

최지욱,임명호,이창화,박진균,손정우,심세훈,유인규,강현수,정범석 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.5

Objectives : Diffuse tensor imaging (DTI) was applied to explore the difference in regional distribution and extent of white matter (WM) abnormalities in boys with Attention-deficit/hyperactivity disorder (ADHD) versus boys with comorbid ADHD and tic disorders. Methods : Fifteen boys with ADHD (mean age 9.3 +1.8), 24 ADHD boys with chronic tic disorder or Tourette's disorder(9.9 =b 1.2) and 9 age-, gender-matched controls (9.2 d= 1.8) received DTI assessments. Fractional Anisotropy (FA) maps of WM were compared between groups with a voxel-wise analysis after intersubject registration to MNI space. Results : Bo groups, ADHD group and ADHD with tic disorder group, commonly showed decreased FA than healthy control group in left cerebellar middle peduncle and right frontal lobe, increased FA in right middle occipital WM. In the common areas of left cerebellar middle peduncle and right middle occipital WM, comorbid group showed broader areas of significant FA. The comorbid group also showed increased FA in right cerebellar peduncle, additionally. Conclusion : The findings in ADHD group support previous ADHD hypothesis of the functional abnormalities in corticocerebellar circuit, and suggest that ADHD might have more complicated pathology of neuronal circuit including occipital visual system. The comorbid group showed common areas of overlapping but more extensive abnormalities and also had additional WM abnormalities. ADHD with chronic tic disorders may represent a severe form of ADHD with additional regions of abnormal connectivity.

1~2기 본태성 고혈압 환자들에서 Imidapril 대 Enalapril의 항고혈압 효과를 평가하기 위한 무작위, 이중맹검 임상시험

최영진,손대원,김용진,이홍자,채인호,김효수,김철호,오병희,이명묵,박영배,채윤식,이영우 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.11

폐경후 여성에서 Estradiol Patch(DH-ETDS)의 임상효과

최영길,김성운,양인명,김진우,김영설,김광원 최신의학사 1993 最新醫學 Vol.36 No.11