Protein kinases have been demonstrated to play a crucial role in cell signaling. Their potential for drug targeting and clinical significance have made them a prime focus for treating severe diseases, particularly cancer. One of these ubiquitous enzymes, protein kinase A (PKA), also known as c-AMP Dependent Protein Kinase, regulates numerous processes like cell growth, development, metabolism, and gene expression. In addition, it was found that disruption or mutation of PKA can lead to high-risk health conditions.
Notably, due to its consistent production through recombinant expression, stability, and crystallization ability, PKA has become a pivotal tool in the study of protein kinases. Also, recently, this enzyme has drawn attention as a diagnostic biomarker. Its overexpression and presence in blood plasma have been linked to various forms of cancer [1]. However, the essential nature of cyclic adenosine monophosphate (cAMP) in cellular processes makes PKA an ‘anti-target’ for most protein kinase inhibition strategies [2]. In view of this, to better comprehend the functioning of cAMP, further efforts must be taken to investigate potent and selective protein kinase A inhibitors.
In its search for effective fact-finding tools, our cheminformatics team has developed a new Docking Library comprising over 2,200 small-molecule compounds. This Screening Set employs docking-based techniques against the catalytic alpha subunit of cAMP-dependent protein kinase.
Compound selection
High-throughput virtual screening and molecular fitting were performed on two protein structures 1XH6, 3MVJ against the Life Chemicals HTS Compound Collection. The compound selection was refined using in-house MedChem filters to remove PAIN and toxic and reactive molecules, resulting in over 2,200 drug-like screening compounds.
Key features:
- Method: high-throughput virtual screening (docking), molecular fitting
- X-ray data used: 1XH6, 3MVJ
- Constraints: H-bonds (Val123, Thr183, and Glu121)
- Filters used: PAINS, toxic, reactive
- Number of compounds selected: 2,240
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Fig.1. Example of PKA-ligand complex obtained after docking calculations for compound F1609-1195 from the Life Chemicals PKA Focused Library.
References
- Cho YS, Park YG, Lee YN, Kim MK, Bates S, Tan L, Cho-Chung YS. Extracellular protein kinase A as a cancer biomarker: its expression by tumor cells and reversal by a myristate-lacking Calpha and RIIbeta subunit overexpression. Proc Natl Acad Sci U S A, 2000, 97(2), 835-840.
- Taylor S. S., Zhang P. et. al. Biochimica et Biophysica Acta, 2013, 1834, pp. 1271–1278.
- Freeman-Cook K. D., Autry C. et. al. J. Med. Chem. 2010, 53, pp. 4615–4622