De novo design and optimization of Aurora A kinase inhibitors

Tiago Rodrigues; Filip Roudnicky; Christian P. Koch; Takayuki Kudoh; Daniel Reker; Michael Detmar; Gisbert Schneider

doi:10.1039/c2sc21842a

De novo design and optimization of Aurora A kinase inhibitors

Tiago Rodrigues, Filip Roudnicky, Christian P. Koch, Takayuki Kudoh, Daniel Reker, Michael Detmar, Gisbert Schneider

Graduate School of Natural Science and Technology

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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	https://doi.org/10.1039/c2sc21842a
Publication status	Published - Mar 2013

ASJC Scopus subject areas

Chemistry(all)

Access to Document

10.1039/c2sc21842a

Fingerprint Dive into the research topics of 'De novo design and optimization of Aurora A kinase inhibitors'. Together they form a unique fingerprint.

Cite this

@article{d0ff1d18f3b641589de044595943ae22,

title = "De novo design and optimization of Aurora A kinase inhibitors",

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.",

author = "Tiago Rodrigues and Filip Roudnicky and Koch, {Christian P.} and Takayuki Kudoh and Daniel Reker and Michael Detmar and Gisbert Schneider",

year = "2013",

month = mar,

doi = "10.1039/c2sc21842a",

language = "English",

volume = "4",

pages = "1229--1233",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

number = "3",

}

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 -

De novo design and optimization of Aurora A kinase inhibitors

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this