Preface

Despite major developments in the early diagnosis and understanding of underlying molecular mechanisms, cardiovascular diseases (CVDs) remain the leading cause of death (31% death globally), followed by cancers. The risk of developing CVDs is highest among all non-communicable diseases. It has increased multi-fold with the increase in prevalence of metabolic disorders, including obesity. CVDs affect people of all regions and all ages, and there are many socio-demographic risk factors. Despite major basic research in this area, translating laboratory discoveries into therapeutic interventions remains a major challenge, and only a handful of drugs have reached to clinical application. Thus drug development against cardiovascular diseases has many unique challenges which large pharmaceutical companies are often not willing to address. The 6^th volume of the book series entitled, “Frontiers in Cardiovascular Drug Discovery” is a compilation of five reviews on diverse topics, including translational research towards improved drugs, various molecular pathways and biomarkers to be targeted for the drug discovery as well as challenges in cardiovascular drug development.

The review by Pratiti et al is focused on the piperazine-based drug ranolazine for the treatment of various cardiovascular diseases. Ranolazine was initially developed as an oral antianginal medicine, and later identified as a versatile cardiovascular drug against various indications. The authors have provided a detailed account of translational research work carried out on ranolazine for a whole range of other CVDs. In the second chapter Zhang et al have emphasized the importance of Rho/Rho kinase (ROCK) as an important drug target. Rho/Rho kinase is related to cardiovascular conditions such as coronary atherosclerosis, hypertension, and heart failure. Selective inhibitors of ROCK can treat many CVDs. This article presents the relationship between various CVDs and Rho/Rho kinase, and thus validates this as a legitimate drug target. Numerous examples of ROCK inhibitors with potential as drugs are also presented.

The review article of G. Mercanoglu and F. Mecanoglu provides a comprehensive account of major challenges and bottlenecks in CVD drug development, that have resulted in a huge vacuum in this drug pipeline. The authors have commented on reasons of a gradual shift of CVD drug development from large pharmaceutical companies to medium pharma industries, small biotech firms and research and development institutions. A field which was historically considered as a “profitable” area of therapeutic research and development now needs support from World Health Organizations and other NGOs. With this background, the authors have provided some logical solutions to overcome the existing problems. Platelet P2Y12 receptor (P2Y12R) for adenosine 5'diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Akaydin et al have discussed various approaches to inhibit P2Y12 receptors for the prevention of platelet aggregation and thrombosis. These inhibitors can also prevent and treat ischemic complications in patients with unstable angina, myocardial infarction and coronary intervention. Various classes of P2Y12 inhibiting drugs and their clinical outcomes are discussed. Kabir et al have contributed a comprehensive review on the nexus of diabetes and cardiovascular diseases such as atherosclerosis, hypertension and myocardial infarction. CVD is the most prevalent cause of mortality in the diabetic population. The authors have also provided a detailed account of the mechanisms of the onset of these diseases. Studies of the molecular mechanisms involved in the progression of CVDs in diabetes as well as biomarker identification can not only contribute to the early diagnosis and prevention of the disease, but it can also help in the novel target identification for anti-diabetic and anti-CVD drug development.

I would like to express our gratitude to all the authors for their scholarly contributions, and for the timely submissions of their reviews. The production team of Bentham Science Publishers also deserves our appreciation for the job very well done. Among them Ms. Mariam Mehdi (Assistant Manager Publications), and Mr. Mahmood Alam (Director Publications) have played a key role in the timely completion of the volume in hand. We sincerely hope that the efforts of authors and production team will help readers in a better understanding of the recent important developments in this key area of therapeutic intervention.