Abstract
We have constructed a very large virtual diversity space containing more than 1013 chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range.
| Original language | English |
|---|---|
| Pages (from-to) | 47-63 |
| Number of pages | 17 |
| Journal | Journal of Computer-Aided Molecular Design |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2005 |
| Externally published | Yes |
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Keywords
- Combinatorial library
- de novo drug design
ASJC Scopus subject areas
- Molecular Medicine
Cite this
A very large diversity space of synthetically accessible compounds for use with drug design programs. / Nikitin, Sergey; Zaitseva, Natalia; Demina, Olga; Solovieva, Vera; Mazin, Evgeny; Mikhalev, Sergey; Smolov, Maxim; Rubinov, Anatoly; Vlasov, Peter; Lepikhin, Dmitry; Khachko, Denis; Fokin, Valery; Queen, Cary; Zosimov, Viktor.
In: Journal of Computer-Aided Molecular Design, Vol. 19, No. 1, 01.2005, p. 47-63.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A very large diversity space of synthetically accessible compounds for use with drug design programs
AU - Nikitin, Sergey
AU - Zaitseva, Natalia
AU - Demina, Olga
AU - Solovieva, Vera
AU - Mazin, Evgeny
AU - Mikhalev, Sergey
AU - Smolov, Maxim
AU - Rubinov, Anatoly
AU - Vlasov, Peter
AU - Lepikhin, Dmitry
AU - Khachko, Denis
AU - Fokin, Valery
AU - Queen, Cary
AU - Zosimov, Viktor
PY - 2005/1
Y1 - 2005/1
N2 - We have constructed a very large virtual diversity space containing more than 1013 chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range.
AB - We have constructed a very large virtual diversity space containing more than 1013 chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range.
KW - Combinatorial library
KW - de novo drug design
UR - http://www.scopus.com/inward/record.url?scp=20344378493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20344378493&partnerID=8YFLogxK
U2 - 10.1007/s10822-005-0097-6
DO - 10.1007/s10822-005-0097-6
M3 - Article
C2 - 16059666
AN - SCOPUS:20344378493
VL - 19
SP - 47
EP - 63
JO - Journal of Computer-Aided Molecular Design
JF - Journal of Computer-Aided Molecular Design
SN - 0920-654X
IS - 1
ER -