한마디
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TISTORY
2010/05/13 15:00
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안녕하세요. TISTORY입니다.
너무 오랜만에 방명록에 전체 인사를 드리는 것 같습니다.
화창한 날씨가 계속 되는 5월, 잘 지내시죠?^^
갑작스런 방문 인사에 놀라신 분들도 계실 것 같습니다.
11일부터 제공하게된 티에디션 기능을 소개하고 이벤트도 알려드리려 글을 남겨드립니다.
관련 공지 : http://notice.tistory.com/1511
티에디션 기능도 이용해보고, 멋진 넷북을 받을 수 있는 기회를 놓치지 마세요~!
감사합니다. -
jinni 2010/03/30 16:52 수정/삭제 댓글쓰기
안녕하세요 !! 초보 개미입니다.
예전에 여기 자주 왔었는데요, 한동안 추천종목 접근이 안되어서 나름대로 투자 했는데
계속 손실만 보다가, 다시 여기로 와보니
비록 기일이 지나서지만, 추천종목을 알수있어서 정말 다행스럽습니다.
추천종목중에서 잘 선택해서 다시 투자해볼 생각입니다. ~!~
추신 : 좋은 자료 감사합니다. ~ -
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우연히 2009/12/01 03:00 수정/삭제 댓글쓰기
어떻게 우연히 들어오게 되었네요
주식손실로 인해서 잠이 안와 인터넷서핑한게 여기로 오게 되었어요^^;
이것저것 관심이 가다가 댓글 남깁니다 -
여유있는남자 2009/11/16 02:12 수정/삭제 댓글쓰기
개미투자자입니다. 우연히 지식검색을 하다가 여기까지 들어오게 되었네요 좋은 정보가 많은거 같아서 공유하고 싶은데
회원 가입하는 곳도 없고 어떻게 하면 여기 회원이 될 수 있을까요?? -
005500 2009/09/28 14:19 수정/삭제 댓글쓰기
삼진제약의 경구용에이즈치료제 관련 소식..NIH.(.미국 국립보건원)으로 부터 받은 자금소식)
아래 내용에 따르면 연구자금을 지원받기위해서 수개월전에 지원신청을 했고.
임퀘스트는 임상승인을 당연하게 생각했다고 보여짐,,
전체적인 내용은 무엇인가요??
ㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡㅡCRISP - A Database of Biomedical Research Funded By the National ... ... As of September 1, 2009, the CRISP system is no longer supported and it will become
unavailable on October 31, 2009. The CRISP system has been replaced by the RePORT
Expenditures and Results (RePORTER) query tool. ... Continue to use CRISP. ...
www.ninr.nih.gov/ResearchAndFunding/FundedNinrGrantsCollaborativeActivities/CrispFile.htm - 10k -
09-21-2009 - Cached
Grant Number: 1R43AI084676-0109
Project Title: Development of Pyrimidinedione NNRTIs With a High Genetic Barrier to Resistance
PI Information: Name Email Title
BUCKHEIT, ROBERT WALTER. rbuckheit@imquest.com PRESIDENT AND CHIEF SCIENTIFIC OFFICER
Abstract: DESCRIPTION (provided by applicant): Although the currently approved NNRTIs (nevirapine, delavirdine, efavirenz, etrivirine) are highly potent, significant improvements in therapeutic utility are still required. A new generation of NNRTIS must be developed which will allow once per day dosing, exhibit significantly reduced toxicity, be amenable to dosing in woman of child bearing age, and possess a significantly higher genetic barrier to resistance selection. NNRTIs being developed by Tibotec (Etrivirine) and Idenix (IDX-899) appear to possess many of these promising therapeutic properties and these compounds are currently approved for use or entering Phase 3 human clinical trials. Structure-activity relationship data obtained with the pyrimidinediones indicates that a next generation pyrimidinedione may also be expected to meet and potentially exceed these necessary properties for a next generation NNRTI and a variety of initial lead compounds have been identified for further development. The pyrimidinediones are amenable to once per day dosing with plasma blood concentrations in excess of 20-times the required EC95 concentration achieved at 24 hours post-dosing. Additionally, ImQuest has initiated studies to optimize the formulation and delivery of IQP-0410 and preliminary results suggest further enhancement to this trough drug concentration. The pyrimidinediones have been dosed in mice, rats and dogs at concentrations of up to 2000 mg/kg/day without any overt or microscopic pathologic signs of toxicity suggesting that the compounds will likely be very safe in humans, and thus may be clinically useful in woman of child bearing age. Most importantly, the pyrimidinediones would be expected to possess an extremely high genetic barrier to resistance based on preliminary antiviral data against common problematic NNRTI-resistant and MDR viruses as well as the defined second mechanism of action of the pyrimidinediones. Though our current lead compound IQP-0410 appears to have favorable activity against these drug resistant strains, additional analogs have been identified with much more potency against drug resistant strains. Among the pyrimidinedione series of molecules, the apparent initial limit to resistance with NNRTI-resistance engendering mutations is approximately 100- to 200-fold since at that concentration level, the replication of NNRTI-resistant virus is suppressed through the entry inhibitory mechanism. Thus, in order to achieve high level resistance to the pyrimidinediones we have shown that multiple mutations must accumulate in the reverse transcriptase AND mutations must appear in both gp120 and gp41, enabling a high genetic barrier to resistance selection. PUBLIC HEALTH RELEVANCE: The overall goal of this proposal is to define new lead therapeutic candidate compounds with the highest possible potency against NNRTI-resistant and MDR viruses. Lead compounds with greater potency against these viruses have been identified through our SAR evaluations, and these compounds will be further modified using standard medicinal chemistry to improve their activity against resistant viruses, to improve their solubility, and to improve their overall oral bioavailability. Enhanced potency of the pyrimidinediones may be achieved by identifying compounds with greater molecular flexibility allowing them to better bind to the hydrophobic NNRTI-binding pocket in the presence of NNRTI resistance-engendering mutations, as well as by identifying modifications which enhance the ability of the compounds to inhibit virus entry. Modifications which improve solubility and bioavailability are also expected to allow enhancements to our dosing regimen to drive further improvements in compound efficacy.
Public Health Relevance:
This Public Health Relevance is not available.
Thesaurus Terms:
There are no thesaurus terms on file for this project.
Institution: IMQUEST BIOSCIENCES
Suite R
FREDERICK, MD 21704
Fiscal Year: 2009
Department:
Project Start: 05-SEP-2009
Project End: 31-AUG-2010
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: ZRG1 -
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