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ilib diverse

Science & Technology

ilib diverse is based on CombiGen

ilib diverse was built upon CombiGen, which has been designed for obtaining compound libraries with an optimal molecular diversity. The algorithms used for efficient parametrization of molecules, the virtual combination of fragments and the efficient identification of chemical features and atoms relevant for molecule construction can be found in reference [1].

High drug-likeness in virtual libraries

In a very early development stage, virtual CombiGen compounds were tested for drug-likeness by a neural network developed at BASF by J. Sadowski and H. Kubinyi [2]. The encouraging result was that more than 93% percent of a sample library possess a drug-like structure while the fraction of known molecules was below 0.1%.

Successful applications

Ilib diverse was used to successfully buil develop in silico a series of potential inhibitors for a new interaction mode of Creatin Kinase, which could partly access the nucleotide binding site. The short synthesis of only four derivatives provided entirely novel hit compounds that reversibly inhibit creatine kinase at micromolar concentrations with a mixed ATP-competitive/noncompetitive mechanism in agreement with the structural model of the inhibited enzyme [3].

References

[1]G. Wolber and T. Langer. CombiGen: A novel software package for the rapid generation of virtual combinatorial libraries. In H.-D. Höltje and W. Sippl, editors, Rational approaches to drug design, pp 390-399. Prous Science, 2000.
[2] J. Sadowski and H. Kubinyi. A Scoring Scheme for Discriminating between Drugs and Nondrugs. J. Med. Chem.; 1998; 41(18) pp 3325 - 3329).
[3]Bretonnet, A.-S.; Jochum, A.; Walker, O.; Krimm, I.; Goekjian, P.; Marcillat, O.; Lancelin, J.-M.; NMR Screening Applied to the Fragment-Based Generation of Inhibitors of Creatine Kinase Exploiting a New Interaction Proximate to the ATP Binding SiteJ. Med. Chem.; 2007; 50(8); 1865-1875.
DOI: 10.1021/jm061460r

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