Abstract
Drug discovery programs urgently seek new chemical entities that meet the needs of a demanding pharmaceutical industry. Consequently, de novo ligand design is currently re-emerging as a novelty-generating approach. Using ligand-based de novo design software, we computationally generated, chemically synthesized and biochemically tested a new arylsulfonamide against Aurora A kinase, a validated drug target in several types of cancer. The designed compound exhibited desired direct inhibitory activity against Aurora A kinase. By chemical optimization we obtained a lead structure exhibiting sustained activity in phenotypic assays. These results emphasize the potential of ligand-based de novo design to consistently deliver functional new chemotypes within short timeframes and limited effort.
| Original language | English |
|---|---|
| Pages (from-to) | 1229-1233 |
| Number of pages | 5 |
| Journal | Chemical Science |
| Volume | 4 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2013 |
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ASJC Scopus subject areas
- Chemistry(all)
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De novo design and optimization of Aurora A kinase inhibitors. / Rodrigues, Tiago; Roudnicky, Filip; Koch, Christian P.; Kudoh, Takayuki; Reker, Daniel; Detmar, Michael; Schneider, Gisbert.
In: Chemical Science, Vol. 4, No. 3, 03.2013, p. 1229-1233.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - De novo design and optimization of Aurora A kinase inhibitors
AU - Rodrigues, Tiago
AU - Roudnicky, Filip
AU - Koch, Christian P.
AU - Kudoh, Takayuki
AU - Reker, Daniel
AU - Detmar, Michael
AU - Schneider, Gisbert
PY - 2013/3
Y1 - 2013/3
N2 - Drug discovery programs urgently seek new chemical entities that meet the needs of a demanding pharmaceutical industry. Consequently, de novo ligand design is currently re-emerging as a novelty-generating approach. Using ligand-based de novo design software, we computationally generated, chemically synthesized and biochemically tested a new arylsulfonamide against Aurora A kinase, a validated drug target in several types of cancer. The designed compound exhibited desired direct inhibitory activity against Aurora A kinase. By chemical optimization we obtained a lead structure exhibiting sustained activity in phenotypic assays. These results emphasize the potential of ligand-based de novo design to consistently deliver functional new chemotypes within short timeframes and limited effort.
AB - Drug discovery programs urgently seek new chemical entities that meet the needs of a demanding pharmaceutical industry. Consequently, de novo ligand design is currently re-emerging as a novelty-generating approach. Using ligand-based de novo design software, we computationally generated, chemically synthesized and biochemically tested a new arylsulfonamide against Aurora A kinase, a validated drug target in several types of cancer. The designed compound exhibited desired direct inhibitory activity against Aurora A kinase. By chemical optimization we obtained a lead structure exhibiting sustained activity in phenotypic assays. These results emphasize the potential of ligand-based de novo design to consistently deliver functional new chemotypes within short timeframes and limited effort.
UR - http://www.scopus.com/inward/record.url?scp=84876736732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876736732&partnerID=8YFLogxK
U2 - 10.1039/c2sc21842a
DO - 10.1039/c2sc21842a
M3 - Article
AN - SCOPUS:84876736732
VL - 4
SP - 1229
EP - 1233
JO - Chemical Science
JF - Chemical Science
SN - 2041-6520
IS - 3
ER -