Endogenous protein kinase inhibitors are essential for a wide range of physiological functions. These endogenous inhibitors may mimic peptide substrates as in the case of the heat-stable protein kinase inhibitor (PKI), or they may mimic nucleotide triphosphates. Natural product inhibitors, endogenous to the unique organisms producing them, can be potent exogenous inhibitors against foreign prot...

coronary heart disease is the leading cause of death and disability in adults. the association between acute coronary syndrom (acs) and elevated serum high sensitivity c-reactive protein (hscrp) suggests that chronic inflammation of the coronary arterial wall may play an important role. a number of drugs used in the treatment of cardiovascular disease reduce serum crp. it* is therefore possible...

Antiproliferative protein (APP) isolated from conditioned media of two androgen-independent prostatic carcinoma cell lines, PC3 and Du-145 was shown to inhibit selectively cell proliferation of androgen-dependent prostate cancer cell line LNCaP in a dose dependent manner. This protein was further purified with HPLC using hydrophobic interaction column (phenyl 5PW) and was used to study the modu...

Kinase-mediated resistance to antibiotics is a significant clinical challenge. These enzymes share a common protein fold characteristic of Ser/Thr/Tyr protein kinases. We screened 14 antibiotic resistance kinases against 80 chemically diverse protein kinase inhibitors to map resistance kinase chemical space. The screens identified molecules with both broad and narrow inhibition profiles, provin...

Predicting off-targets by computational methods is getting increasing importance in early drug discovery stages. We herewith present a computational method based on binding site three-dimensional comparisons, which prompted us to investigate the cross-reaction of protein kinase inhibitors with synapsin I, an ATP-binding protein regulating neurotransmitter release in the synapse. Systematic pair...

Treatment of BRAF-mutant colorectal cancer (CRC) traditionally represents an unmet need, mainly due to its unfavourable prognostic outlook, limited options for targeted treatment and scarce benefit from epithelial growth-factor receptor (EGFR) inhibitors. Recently, the development BRAF V600E inhibitors has expanded therapeutic armamentarium, al...