The modification of lead-compound aimed to the increasing activity, decrement toxicity or improvement selectivity is one most important methods used for elaboration novel medications. Natural compounds, approved investigational drugs just compounds with proved biological activity could be lead-compound. Often chemical lead directed at enhancement ligand-biological target interactions. Abovement...

The concomitant development of in silico screening technologies and of three-dimensional information on therapeutically relevant macromolecular targets makes it possible to navigate in the structural proteome and to identify targets fulfilling user-defined queries. This review illustrates some in-house recent advances in the development of target libraries and how they can be browsed to unravel...

We report here on the screening of a fragment library against a G-quadruplex element in the human c-MYC promoter. The ten fragment hits had significant concordance between a biophysical assay, in silico modelling and c-MYC expression inhibition, highlighting the feasibility of applying a fragment-based approach to the targeting of a quadruplex nucleic acid.

Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.

background: resistance to antiepileptic drugs as well as intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (dha), make it as a good candidate for designing and development of the new anticonvulsant medications. methods: ten dha-based...

The “one drug – one target – one disease” paradigm in drug discovery has been reconsidered during the last decade. This paradigm change was mainly caused by high attrition rates in drug approvals due to toxicity and lack of efficacy. Computational techniques play an important role in prediction and recognition of novel targets for approved drugs. We will discuss two machine learning approaches ...

BACKGROUND Protein-protein interactions (PPIs) are challenging but attractive targets for small chemical drugs. Whole PPIs, called the 'interactome', have been emerged in several organisms, including human, based on the recent development of high-throughput screening (HTS) technologies. Individual PPIs have been targeted by small drug-like chemicals (SDCs), however, interactome data have not be...

Background: Non-coding RNAs apply regulations on expression or function of a gene. A class of non-coding RNAs, natural antisense transcripts, might overlap with their flanking genes and emerge a new complexity upon regulation. WRAP53, is a natural antisense transcript overlapped in a head-to-head manner on the opposite strand of TP53. It has 3 transcripts of which WRAP53β produ...