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Pharma Congress 2018 & Molecular Medicine 2018
& Psychiatric Disorders 2018 Asian Journal of Biomedical and Pharmaceutical Sciences | ISSN: 2249-622X| Volume 8
International Conference on
PHARMACEUTICS AND NOVEL DRUG DELIVERY SYSTEMS
19th International Conference on
CELLULAR AND MOLECULAR MEDICINE
19th Annual Congress on
PSYCHIATRY AND PSYCHIATRIC DISORDERS
&
&
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
Hiroshi Ohrui, Asian J Biomed Pharmaceut Sci 2018, Volume 8 | DOI: 10.4066/2249-622X-C3-007
EFDA: A VERY EXCELLENT ANTI-HIV
MODIFIED NUCLEOSIDE FROM DESIGN TO
THE CURRENT CLINICAL RESULTS
EFdA prevents the emergence of resistant HIVmutants, and is over 400 times
more active than AZT and several orders of magnitude more active than the
other clinical reverse-transcriptase inhibitor y 2’, 3’-dideoxynucleoside drugs,
very low toxic, very long acting, and very useful for prophylaxis. EFdA is now
under clinical investigation by Merck & Co. as MK-8591. In the beginning, a
general idea for the development of anti-viral modified nucleosides will be
resented, and next, the development of EFdA is discussed and then the current
results of the clinical trials reported by Merck will be presented. For the design
of the modified nucleoside which could solve the critical problems that the
clinical drugs have (emergence of drug-resistant HIV mutants, adverse effect
by drugs, necessity to take considerable amount of drugs), four working
hypotheses were proposed. They are the way to prevent the emergence of
drug-resistant HIV mutants, the way to decrease the toxicity of modified
nucleosides, the way to provide the modified nucleoside with stability to both
enzymatic and acidic glycolysis for long acting and it is possible to develop
selectively active to HIV and very low toxic to human based on the difference
of the substrate selectivity between RT and human nucleic acid polymerases.
4’-C-substituted-2’-deoxy nucleoside (4’SdN) was designed as the nucleoside
which could satisfy these hypotheses. The study based on 4’SdN successfully
developed EFdA [modified at the two position (2 and 4’) of the physiologic
2’-deoxyadenosine] having extremely excellent anti-HIV activity.
Biography
Hiroshi Ohrui has joined Riken in the year 1966 and
moved to Tohoku University (1981) and to Yoko-
hama University of Pharmacy (2006). He worked
for Dr J J Fox at Sloan-Kettering Institute for Can-
cer Research (1972-1973) and Dr J G Moffatt at
Syntex Research (1973-1974). He received several
awards including The Japan Society for Analyti-
cal Chemistry Award (2004), and Japan Academy
prize (2010). His research interests cover organic
synthesis, chemical biology and chiral discrimina-
tion.
Hiroshi Ohrui
Yokohama University of Pharmacy, Japan