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Core/Capsid Inhibitors 기반 в형 간염 치료제 개발 현황 및 전망
김균환 ( Kyun-hwan Kim ) 대한간학회 2021 임상연구방법론워크숍 Vol.2021 No.1
More than 240 million people are chronically infected with hepatitis в virus (HBV), with some 600,000 deaths per year attributed to the virus. Chronic HBV infection is associated with significant morbidity and mortality, fibrosis, cirrhosis, end-stage liver diseases and primary hepatocellular carcinoma (HCC). However, the current antiviral drugs can efficiently control but not eliminate HBV in the carriers at risk to develop liver diseases and cancer. HBV patients often require lifelong therapies and cure is still a challenging goal because HBV establishes a stable nuclear persistence form, the so-called HBV cccDNA, in infected hepatocytes. Eliminating HBV cccDNA is a critical issue if we want to cure HBV infection. Recent advances in basic HBV sciences have heralded a new horizon of innovative therapeutic approaches to the possibility of a functional cure of chronic HBV infection. These approaches include inhibitors of viral entry, cccDNA modulators, interfering RNA targeting viral RNAs, novel polymerase or ribonuclease H inhibitors, core protein allosteric modulators and capsid assembly modulators (capsid inhibitors), drugs interfering with HBx function, drugs targeting viral and HBsAg egress, or agents restoring the host immunity against HBV. Among these approaches, novel direct acting capsid assembly inhibitors or modulators have an important impact in HBV replication cycle. They can interfere with several steps of the HBV replication cycle including capsid assembly, reverse transcription, as well as pgRNA and polymerase protein packaging. These molecules may also affect intracellular trafficking of relaxed circular DNA in the nucleus, virus assembly by disrupting its inter-action with envelope proteins, and core binamg to cccDNA. Two mam classes or core assembly modulators have been developed, including class I heteroarylpyrimidines (HAP), and class II phenylpropenimides (pp) or sulfamoylbenzamide (SBA) and derivatives. The current core/capsid inhibitor in development for chronic hepatitis в are summarized in Table 1. In this talk, I will review the current state of core/capsid inhibitors. Especially, I will focus on the action mechanisms of capsid inhibitors in detail and introduce the limitations of these strategies. It is very likely that a combination of drugs currently in development will need to be employed to successfully cure HBV infection.
CIS 태양전지용 이원 화합물CuxSe 나노입자를 이용한 CuxSe 박막 제조
김균환(Kim, Kyun-Hwan),안세진(Ahn, Se-Jin),윤재호(Yun, Jae-Ho),곽지혜(Gwak, Ji-Hye),김도진(Kim, Do-Jin),윤경훈(Yoon, Kyung-Hoon) 한국신재생에너지학회 2009 한국신재생에너지학회 학술대회논문집 Vol.2009 No.06
This report summarizes our recent efforts to produce large-grained CIGS materials from porous nanoparticle thin films. In our approach, a Cu_xSe nanoparticle colloid were first prepared by reacting a mixture of CuI in pyridine with Na₂Se in methanol at reduced temperature. purified colloid was sprayed onto heated molybdenum-coated sodalime glass substrates to form thin film. After thermal processing of the thin film under a selenium ambient. Cu_xSe colloid and thin film were characterized by scanning electron microscopy, x-ray diffraction. The optical(direct) band gap energy of Cu_xSe thin films is 1.5 eV.
김균환(Kim, Kyun-Hwan),안세진(Ahn, Se-Jin),윤재호(Yun, Jae-Ho),곽지혜(Gwak, Ji-Hye),조아라(Jo, A-Ra),김도진(Kim, Do-Jin),윤경훈(Yoon, Kyung-Hoon) 한국신재생에너지학회 2009 한국신재생에너지학회 학술대회논문집 Vol.2009 No.11
Chalcopyrite semiconductor CuInSe₂ nanoparticles were prepared using a low temperature colloidal route by reacting the starting materials (CuI, InI₃ and Na₂Se) in solvents. After synthesised CuInSe₂ nanoparticles precursors were mixed with organic binder for the viscosity of the precursor slurry to be suitable for the doctor blade method. The mixture of CuInSe₂ and binder was deposited onto molybdenum-coated sodalime glass substrates to form thin film. The precursor thin films were preheated on the hot plate to remove remaining solvents and binder material. After subsequent thermal processing of the thin film under a selenium ambient, CuInSe₂ absorber layer with grain size significantly lager than that of the nanoparticles was formed.
김균환 ( Kyun-hwan Kim ) 대한간학회 2017 임상연구방법론워크숍 Vol.2017 No.1
지난 수십년 동안 B형간염 바이러스 (HBV) 치료제는 뉴클레오사이드 유도체를 중심으로 많은 발전을 하여 왔다. 그러나 이들은 모두 HBV 중합효소의 저해제들로서 약재 내성 돌연변이의 출현 등 한계를 가지고 있고, 나아가서 하나의 바이러스 단백질을 타겟으로 하여 개발된 것이기 때문에 근본적으로 칵테일 요법의 효율성이 떨어지는 문제점을 가지고 있다. 따라서, HCV나 HIV처럼 효과적인 칵테일 요법이 도입되기 위해서는 중합효소 외의 다른 HBV 바이러스 단백질이나 생활사를 타겟으로 하는 약물의 개발이 필수적이며 수요도 점점 늘어나고 있다. 이러한 요구에 부응하여 최근에 바이러스의 캡시드 형성을 저해하는 약물의 개발이 한창 진행중에 있으며, 중합효소의 RNAse H 기능을 저해하는 약물도 개발 중에 있다. 이 외에도 HBV의 수용체인 NTCP 저해제 및 siRNA를 기반으로 하는 약물 등의 개발도 진행 중이다. 본 발표에서는 오랫동안 HBV 기초 연구를 수행한 경험을 바탕으로 현재 진행되고 있는 약물들의 기전 및 그들의 한계에 대해 논의하고자 한다. 또한, 현재 진행 중인 캡시드 형성 저해제 연구 개발 경험을 소개하고, 궁극적으로 HBV의 완치를 위해서는 HBV cccDNA를 제거하여야 하는데, 어떻게 cccDNA를 조절할 수 있는지에 대한 기초 연구도 소개하고자 한다. 이러한 연구들이 성공적으로 수행되기 위해서는 최신 연구 방법과 그를 뒷받침하기 위한 실험재료 및 임상 연구자들 과의 공동연구에 대한 중요성들을 논의하고자 한다.
27 간 이식후 간염면역글로불린과 라미부딘 치료이후에도 급성 재발을 보인 환자에서 연속적인 B형바이러스 유전자 분석
김균환 ( Kyun Hwan Kim ),한광협 ( Kwang Hyub Han ),이광희 ( Kwang Hee Lee ),장혜영 ( Hye Young Chang ),윤영준 ( Young Joon Yoon ),박영년 ( Young Nyun Park ),김순일 ( Soon Il Kim ),전재윤 ( Chae Yoon Chon ),문영명 ( Young Myoung 대한소화기학회 2002 대한소화기학회 추계학술대회 Vol.2002 No.-
김균환 ( Kyun Hwan Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2
Infection of hepatitis B virus (HBV) is a main cause of liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Among the HBV-encoded proteins, the HBV X protein (HBx) has been suspected to be strongly involved in HBV-associated liver pathogenesis. HBx, a virally encoded multifunctional regulator, has been shown to induce apoptosis, anti-apoptosis, proliferation, and transformation of cells depending on the cell lines, model systems used, assay protocols, and research groups. Among the several activities of HBx, the pro-apoptotic function of HBx will be discussed in this review. Given that the disruption of apoptosis pathway by HBx contributes to the liver pathogenesis, a better understanding of the molecular interference in the cellular pro-apoptotic networks by HBx will provide useful clues for the intervention in HBV-mediated liver diseases.