Current Pharmaceutical Design - Volume 22, Issue 46, 2016

Single target based approaches often proved to be unsuccessful in complex multigenic diseases such as cancer or schizophrenia. Multi-target drugs can be more efficacious in this regard by modulating multiple processes in the organism. According to the theory of polypharmacology, bioactive molecules possess characteristic interaction patterns that are responsible for their effects and side-effects and getting acquainted with t Read More

For many years, the “one target, one drug” paradigm has been the driving force behind developments in pharmaceutical research. With the recent advances in molecular biology and genomics technologies, the focus is shifting toward “drug-holistic” systems based approaches (i.e. systems pharmacology). The integration of large and diverse amount of data from chemistry and biology coupled with the development and the Read More

Current computational and mathematical tools are demonstrating the high value of using systems modeling approaches (e.g. Quantitative Systems Pharmacology) to understand the effect of a given compound on the biological and physiological mechanisms related to a specific disease. This review provides a short survey of the evolution of the mathematical approaches used to understand the effect of particular cholesterol-l Read More

Drug discovery is complex and expensive. Numerous drug candidates fail late in clinical trials or even after being released to the market. These failures are not only due to commercial considerations and less optimal drug efficacies but, adverse reactions originating from toxic effects also constitute a major challenge. During the last two decades, significant advances have been made enabling the early prediction of toxic ef Read More

Cancer cell line panels have proved useful disease models to, among others, identify genomic markers of drug sensitivity and to develop new anticancer drugs. The increasing availability of in vitro sensitivity and cell line profiling data sets raises the question of whether this information could be used, and to which extent, to predict the activity of drugs in cancer cell lines and, ultimately, in patients tumors. Drug sensitivity Read More

Treatment of ocular disorders is a challenge due to the difficulty of delivering drugs to the target tissues within the eye at sufficient concentrations to produce a therapeutic effect. The cornea and the blood-retinal barrier, comprising of the retinal pigment epithelium and the retinal capillaries, are the main barriers for delivering drugs to treat diseases in the anterior and posterior parts of the eye, respectively. The eye has a ric Read More

Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess Read More

Breast cancer is the most frequent cancer in women. Despite advances in early detection and treatment, it has the second highest mortality rate after lung cancer. Around 85% of breast carcinomas are ER+; thus, antiestrogens like tamoxifen are beneficial. Although, tamoxifen is useful for many patients, a number of patients respond poorly to initial therapy or recurrence occurs in about 30% of cases, because tamoxifen re Read More

The combined use of a photosensitizing agent, light and dioxygen for the treatment of diseases has become known as photodynamic therapy (PDT) and was first discovered more than one hundred years ago. Over the years, PDT has proven its potential for the treatment of malignant and non-malignant lesions in addition to classical cancer therapy in numerous clinical studies, but application as a routine method is still limited. I Read More

Background: This work aimed to evaluate the effects of genistein treatment in Collagen Induced Arthritis (CIA) mouse model. Methods: CIA was elicited in DBA/1 Mice by an intradermal injection of 100 μL of an emulsion of bovine type II collagen (CII) in isovolumic incomplete Freund’s adjuvant (IFA) at the base of the tail. Twenty-one days later, a second injection of CII in IFA was administered at the base of the tail. After Read More

Earlier we reported the identification of diarylpyrimidine-quinolone hybrids as a new class of HIV-1 NNRTIs. A few of these hybrids displayed moderate inhibitory activity against wt HIV-1 replication at submicromolar level, however, all of them lacked inhibitory activity against the double mutant virus (K103N/Y181C), which is the most prevalent NNRTI resistant-associated double mutant observed in the clinic. In the presen Read More

Background: Cyclodextrin-based nanosponges are hyper-cross-linked supramolecular architectures. Similar to the parent compound they are derived from, they have been shown to possess the ability to form inclusion and non-inclusion complexes with drugs of different polarities, enzymes, proteins, peptides and macromolecules. Cyclodextrins only form inclusion complexes with hydrophobic guest molecules, while Read More