Current Medicinal Chemistry - Volume 24, Issue 29, 2017

Background: Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. Conclusion: In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs.

Background: Rare diseases are often serious, life-threatening and debilitating group of disorders. Nowadays, there are approximately 8,000 rare diseases and it is estimated that 350 million people are affected by these conditions worldwide. Unfortunately, rare diseases are quite complex and chronic, only a small number of these diseases can be relevantly diagnosed and treated, and lifelong treatment is often required. Objective: The purpose of this mini review is to explore the issue of rare diseases, describe their classification, discuss the current treatment and management and set future research in this field. Methods: The methods applied in this review include literature review of the world's acknowledged databases such as PubMed, Springer and Web of Science, especially in the period of 2000 to 2015. Furthermore, a method of comparison and evaluation of the findings from the relevant sources is used. Results: The findings confirm that rare diseases are still quite difficult to diagnose due to their comorbidities. Once they are diagnosed, they demand costly and long-term treatment, which raises concerns of national governments. Conclusion: Therefore more research should be done in the space of rare diseases in order to broaden knowledge about them, their diagnosis and treatment, which will then lead to better training of medical staff, and ultimately will benefit the patients.

Background: During lead identification and optimization, the advancement criteria may be driven based on scientific principles, prior experiences, and/or by examining the path paved by approved drugs. However, accessing the discovery data on physicochemical and ADME properties of the approved kinase inhibitors is a monumental task as these are either scattered in the literature or have not been published. Objective: Our goals were: 1) To compile the relevant data on all kinase inhibitors approved prior to 2016 for easy access by the biopharmaceutical community, 2) To provide a retrospective analysis to highlight trends and attributes which may have contributed to the “developability” of these drugs, and 3) To ignite focused debates on what constitutes “actionable”, “nice-to-have”, and unnecessary data. Such debates bring about more clarity on stage appropriateness of different types of information and prevent confusion due to abundance of unnecessary data, leading to more efficient and less costly drug discovery programs. Methods: A careful and thorough analysis of different bodies of data such as published manuscripts, and available regulatory documents were employed. Results: We were able to assemble a large body of data on the first thirty kinase inhibitors approved by US FDA since 2001. Conclusion: In conclusion, we have compiled physicochemical and ADME data on the first 30 approved kinase inhibitors and provided our retrospective analysis, which we hope is helpful in constructing advancement criteria in discovery programs. The examination of this data provides an opportunity to develop an opinion on data prioritization and stage appropriateness of assays.

Background: Diabetic nephropathy (DN) is an important diabetic microvascular complication, and it is becoming the leading cause of end-stage renal disease worldwide. Unfortunately, there are no effective therapies to treat established DN. Therefore, new therapeutic targets are urgently required. Accumulating studies indicate that mitochondrial dysfunction is central to the pathogenesis of DN, and therapies targeted mitochondria might effectively delay the progression of DN. Method: A structured search of previously research literature about mitochondrial structure and function, mitochondrial DNA, mitochondrial biogenesis, mitochondrial dynamics change, mitophagy, mitochondrial ROS, mitochondrial apoptosis and therapies targeted mitochondria has been performed in several databases. Result: 176 papers were included in this review, the results from these papers indicated that mitochondrial dysfunction is a pivotal issue for the development of DN, such as elevated oxidative stress induced by disorders of the mitochondrial respiratory chain complex and mitochondrial dynamic disorders, mutation of mitochondrial DNA, mitochondrial abnormal biogenesis, mitochondrial excessive fission, mitochondrial ROS overproduction. In addition, several therapeutic agents targeting the mitochondria (e.g mitochondrial ROS modulators, mitochondrial fragmentation inhibitors and mitochondrial biogenesis activators) have shown perfect therapeutic effect and security for DN. Conclusion: The finding of this review has further confirmed the vital role of mitochondrial dysfunction in the progression of DN, management strategies for recovering the normal mitochondrial function will offer potential novel therapeutic targets for DN.

Fibrosis occurs in a variety of organs and frequently brings great harm to patients, even contributes to their death. Despite great efforts made in the field of fibrosis over the past decades and considerable understanding of the pathogenesis of fibrotic reactions attained, there is still lack of effective anti-fibrotic treatments. A growing body of evidence indicates a significant anti-fibrotic potential of activated soluble guanylate cyclase (sGC), which emphasizes the importance of sGC in fibrogenesis of diverse organs including skin, kidney, liver and lung. While sGC has been well known for its role in the regulation of vascular tone and vascular remodeling, its possible implication in fibrosis remains to be illustrated. Emerging evidence in recent years provides new insights into anti-fibrotic effect of sGC stimulation by blocking non-canonical TGF-β signaling. In this review we will discuss the key role of sGC and its mechanism of action in fibrosis. Herein, sGC signaling pathway may represent a promising target for treating tissue fibrosis.