The new class of the human protein kinase ASK1 inhibitors has been identified

2011 Apoptosis signal-regulating kinase 1 (ASK1) has recently emerged as an attractive therapeutic target for the treatment of cardiac and neurodegenerative disorders. The selective inhibitors of ASK1 may become important compounds for the development of clinical agents. We have identified the ASK1 inhibitor among 3H-naphtho[1,2,3-de]quinoline-2,7-diones using receptor-based virtual screening. In vitro kinase assay revealed that ethyl 2,7-dioxo-2,7-dihydro-3H-naphtho[1,2,3-de]quinoline-1-carboxylate (NQDI-1) inhibited ASK1 with a Kі of 500 nM. The competitive character of inhibition is demonstrated in Lineweaver-Burk plots. In our preliminary selectivity study this compound exhibited strong specific inhibitory activity toward ASK1. Reference: Volynets GP, Chekanov OM, Synyugin AR, Golub AG, Kukharenko OP, Bdzhola VG, Yarmoluk SM. Identification of 3H-Naphtho[1,2,3-de]quinoline-2,7-diones as Inhibitors of Apoptosis Signal-Regulating Kinase 1 (ASK1) http://pubs.acs.org/doi/abs/10.1021/jm200117h

 

The new class of highly potent ATP-competitive inhibitors of the human protein kinase CK2 has been identified

2011 We have discovered a novel family of ATP-competitive inhibitors of CK2 using chemistry-based optimization. A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC50 values are 0.1 and 0.125 µM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2. Reference: Golub AG, Bdzhola VG, Briukhovetska NV, Balanda AO, Kukharenko OP, Kotey IM, Ostrynska OV, Yarmoluk SM. Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2. Eur. J. Med. Chem. 2011; doi:10.1016/j.ejmech.2010.12.025.

 

New project STSU-NASU has started

2010 In September, 2010 started the Project: STSU-NASU № 5218 «Rational search for inhibitors of aminoacyl-tRNA synthetases with selective action against causative agent of tuberculosis 2010-2012». At the first step was developed the 3D model of M. tuberculosis Leu-tRNA synthetase applying the methods of homology modeling. This model will be used for virtual screening of small-molecule compounds library.

 

VI International Conference on Protein Kinase CK2

2010 Andriy Golub and Volodymyr Bdzhola participated in the VI International Conference on Protein Kinase CK2 (07-10 September, 2010, Cologne, Germany). Our collaborators familiarized themselves with the last achievements in the field of rational design of protein kinase CK2 inhibitors. Our scientists introduced oral presentation «New Compounds Inhibiting an Old Kinase».

 

III International Symposium Methods and Applications of Computational Chemistry

2009 Andriy Golub and Volodymyr Bdzhola presented their report in the ІІІ International Symposium Methods and Applications of Computational Chemistry that took place from June, 28, till July, 2, 2009, in Odessa, Ukraine. At the Conference our scientists represented oral presentation «Computer-aided desing of novel protein kinase CK2 inhibitors».

 

Thesis for Philosophy Doctor Degree in Biology

23.09.2008 Kyiv, Ukraine Member of Molecular Design group, Olexander Yakovenko, has successfuly obtained PhD degree in Biology (speciality: Biotechnology). His thesis is related to development of technology of organic molecules to biomolecular targets affinity estimation in field of high-throughput receptor-based in silico screening. We congratulate our colleague with this remarkable achievement.

 

Inhibitors of Protein Kinases (IPK 2005) Conference

25.06.2005 - 29.06.2005 Warsaw, Poland Volodymyr Bdzhola, Andriy Golub and Olexander Yakovenko took part in the 4th International Conference on Inhibitors of Protein Kinases and Workshop Modelling of Specific Molecular Recognition Processes (June 25-29, 2005, Warsaw, Poland). On the Conference Otava researchers represented two poster presentations: Evaluation of 3-Carboxy-4-(1H)-Quinolones as Inhibitors of Human Protein Kinase CK2 Implementation of orbital graph model for partial atom charges definition in virtual screening technique

Cluster for distributed quantum and molecular mechanic calculations

2005 In 2005 8-node cluster (P4 3.2GHz, 1Gb of memory, Linux OS) for distributed quantum and molecular mechanic calculations was assembled and launched. At the moment cluster involved in virtual screening and molecular dynamics simulation tasks, which are performed in the framework of the project “Development of Protein Kinase Inhibitors”.

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