Medicinal Chemistry Letters Research Articles

Bibliometric Analysis and Systemic Review of Cantharidin Research Worldwide.

Cantharidin (CTD), a natural toxic compound from blister beetle Mylabris, has been used for cancer treatment for millenary. CTD and its analogs have become mainstream adjuvant drugs with radiotherapy and chemotherapy in clinical applications. However, the detailed pharmacology mechanism of CTD was not fully elucidated. Publications of CTD were collected from the Web of Science Core Collection database from 1991 to 2023 using CiteSpace, VOSviewer, and Scimago Graphica software. A total of 1,611 publications of CTD were mainly published in China and the United States. The University of Newcastle has published the most researches. Mcclusey, Adam, Sakoff, Jennette, and Zhang, Yalin had the most CTD publications with higher H. Notably, CTD researches were mainly published in Bioorganic & Medicinal Chemistry Letters and the Journal of Biological Chemistry. Cluster profile results revealed that protein phosphatase 2A (PP2A), human gallbladder carcinoma, Aidi injection, and cell apoptosis were the hotspots. Concentration on the pharmacology function of PP2A subunit regulation, hepatotoxicity, nephrotoxicity, and cardiotoxicity mechanism should be strengthened in the future. Bibliometric analysis combined with a systemic review of CTD research first revealed that PP2A and CTD analogs were the knowledge base of CTD, and PP2A subunit regulation and toxic mechanism could be the frontiers of CTD.

Novel Small Molecule and Peptide Inhibitors of CREB in Leukemia Cells

Background: Acute Lymphoblastic Leukemia (ALL) and Acute Myelogenous Leukemia (AML) account for nearly 45% of all childhood cancer. Current therapy for acute leukemia results in significant morbidity and late complications in children. Therefore, more effective and less toxic therapies to treat leukemia are needed. Previous work in our laboratory has identified CREB (cAMP Response Element Binding Protein), a transcription factor that promotes cell proliferation and survival in acute leukemia, is overexpressed in primary ALL and AML cells and is a potential target for therapy. We have investigated small molecules and peptides to inhibit the critical interaction between the phosphorylated KID (Kinase-Inducible) domain of CREB and the KIX (KID-interacting) domain of the coactivator CBP (CREB Binding Protein). Methods: We assessed a library of previously untested alpha-mimetic compounds from ChemDiv designed to mimic interactions between α-helices and protein surfaces for predicted interaction with a shallow hydrophobic groove on the interaction surface of KIX. We interrogated the 24,737 compounds in the library using rigid-receptor ligand docking, followed by induced-fit ligand docking of the top compounds using two different software, MOE and Schrodinger's Bioluminate. The top 50 binding poses from each software's rankings were combined to yield 87 candidate alpha-mimetic molecule inhibitors. In addition to our screen of small molecules, we have designed peptide inhibitors that closely mimic the αB helix of pKID. We investigated two methods to enhance the stability and cell-penetrating ability of our peptides: hydrocarbon stapling and the utilization of a rigid scaffold from the scorpion toxin peptide BmBKTtx1. Based on the calculated binding scores and locations, the most promising chimeric peptide designs were further investigated for binding stability using 500 nanosecond molecular dynamics (MD) simulations modeling their interaction with KIX. Results: The binding poses of the final set of small molecules were visually inspected for occupation of key hotspots on the pKID:KIX interaction surface, including the location of the phosphorylation sight of KID. Of the 87 molecules and their binding poses, only 21 of them (24%) obstructed fewer than two of the three hotspots chosen for the analysis. Moreover, 80 of the molecules (92%) extended into the hydrophobic pocket, the most critical hotspot. The multi-residue construction of this pocket likely contributed to the high similarity in interaction fingerprint between these molecules and pKID; occupation of this pocket can serve as a good indicator of strong ligand binding to KIX in future assays. The most-promising peptide designs using the scorpion toxin scaffold were assessed with MD simulations and compared to a control peptide comprised primarily of the αB helix of pKID. The chimeric peptides showed increased binding stability over the control peptide with an average RMSD of 6.8Å vs. 12.5Å, illustrating the benefits of the stability afforded by the scorpion scaffold design. Several of the hydrocarbon stapled peptides were tested in vitro using fluorescence polarization (FP) assay developed by our lab (Chae et al. Bioorganic & Medicinal Chemistry Letters, 2019) and in AML HL-60 and KG-1 cells and were shown to have growth inhibitory effects by Cell-Titer Glo Assays. Discussion: These small molecules and scorpion toxin-derived peptides represent novel candidate inhibitors of the pKID:KIX interaction implicated in leukemia. Based on promising results from our in silico analyses of these inhibitors, we have obtained ten structurally diverse alpha-mimetic small molecules and three chimeric peptides and aim to test their efficacy in vitro using the FP assay. Furthermore, we will obtain high resolution cryo-EM structures of successful compounds and peptides bound to the KIX domain using a double-shell protein scaffold (Zhang et al. ACS Central Science, 2022), and use these structures for further refinement of the inhibitors. The development of new inhibitors for the pKID:KIX interaction promises to reveal insights into the structural relationship between the two domains and the basis for effective, targeted leukemia therapeutics.

An Innovation 10 Years in the Making: The Stories in the Pages of ACS Medicinal Chemistry Letters.

Innovation in medicinal chemistry has been at the heart of ACS Medicinal Chemistry Letters since the journal's founding 10 years ago. In his inaugural editorial, Editor-in-Chief Dennis Liotta laid out a vision for the journal to become the "premier international journal for rapid communication of cutting-edge studies," and, after 10 years, it has become exactly that. The great hope of drug discovery scientists is that their innovations will lead to new therapeutics to treat unmet medical needs. In the spirit of innovation and in celebration of the recent 10th anniversary of ACS Med. Chem. Lett., we highlight five therapeutics that were first reported or first comprehensively characterized within ACS Med. Chem. Lett.. This overview also serves to introduce the expansion of the scope of the Innovations article type to include Topical Innovations. With this extension, the journal hopes to provide a forum to showcase concise (rather than comprehensive) reviews of topics that are both timely and of great interest to the medicinal chemistry community. Moreover, these articles will emphasize the next steps to move the field toward new areas of interest in medicinal chemistry. Appropriate topics might include case studies of clinical candidates or approved drugs, new assay technologies in drug discovery, novel target classes, and innovative new approaches towards modulation of human physiology. Since its founding 10 years ago, ACS Med. Chem. Lett. has established itself as a venue for the rapid communication of studies in medicinal chemistry and drug discovery. There have been several drugs and clinical candidates that were first reported or first comprehensively characterized in ACS Med. Chem. Lett. In celebration of the 10th anniversary of ACS Med. Chem. Lett. this Topical Innovations article highlights five of these compounds: Ivosidenib, Siponimod, Glasdegib, Parsaclisib, and Dabrafenib.

The Potential of Medicinal Plants and Bioactive Compounds in the Fight Against COVID-19

The Potential of Medicinal Plants and Bioactive Compounds in the Fight Against COVID-19

Writing Your Next Medicinal Chemistry Article: Journal Bibliometrics and Guiding Principles for Industrial Authors.

Writing scientific articles is immensely rewarding but challenging. This Perspective provides the medicinal chemist with background and advice on the art and process of writing manuscripts and complements the instructions to authors provided by journals. Included are many tips that we wish we had known when we first started writing. Bibliometric data from seven medicinal chemistry journals between 2000 and 2019 are collated including Bioorganic and Medicinal Chemistry Letters and the Journal of Medicinal Chemistry. Although the overall number of articles has doubled, the output from 23 large pharma companies in the past decade has dropped significantly. Commentary is given on the entire process of writing original scientific articles, opinion articles, and reviews. Examples from our own papers and experience are shared including what typically motivates the writer, challenges commonly encountered, and how we find time to write. Finally, the benefits derived from much wider publishing of industrial medicinal chemistry are described.

Application of Bibliometric Analysis to Letters Journals in Organic Chemistry

ABSTRACT Subject librarians are well-positioned to apply and teach searching techniques using online library resources for assisting researchers and scholars on where to publish. A bibliometric analysis was used to compare four premier letters journals in organic chemistry: Bioorganic & Medicinal Chemistry Letters, Letters in Organic Chemistry, Organic Letters, and Tetrahedron Letters. The objective of this study is to develop a routine methodology for evaluating and comparing journals with a similar scope based on researchers’ immediate needs. The study provides a practical guide to help organic chemists decide where to submit a short article for publication. For initial comparative purposes, general parameters, such as subscription rate, open access availability and article processing charge, field categories, language, maximum page length, citation style, peer-review type, review time, publication frequency, impact factor, journal h-index, acceptance rate, and database coverage were obtained from various online resources. Between 1999 and 2016, a total of 20,675 articles from Bioorganic & Medicinal Chemistry Letters, 1,732 articles from Letters in Organic Chemistry, 24,889 articles from Organic Letters, and 34,380 articles from Tetrahedron Letters were retrieved from the advanced search option in Web of Science Core Collection (Science Citation Index Expanded). The articles were examined by year, language, country, and organization. The VOSviewer software was employed for an in-depth map analysis of the research topics covered in each journal derived from key terms in article titles. The SciFinder database was used to compare similarities and differences from the articles in each letters journal through Chemical s indexing.

Toward the elucidation of the mechanism for passive membrane permeability of cyclic peptides.

Toward the elucidation of the mechanism for passive membrane permeability of cyclic peptides.

Morphological analysis of MCF-7 cells treated with chalcone derivatives

Morphological analysis of MCF-7 cells treated with chalcone derivatives

Antimicrobial 2-aminothiazolyl quinolones: what is their potential in the clinic?

Antimicrobial 2-aminothiazolyl quinolones: what is their potential in the clinic?

Abstract 1236: Novel androgen receptor inhibitors in triple negative breast cancer

Abstract Triple negative breast cancer (TNBC), which lacks expression of hormone receptors and human epidermal growth factor receptor 2, has the worst prognosis of all breast cancer subtypes, due to inherent chemo-resistance and a lack of therapeutic targets. A subset of TNBC has been shown to express androgen receptor (AR) but despite promising pre-clinical data, clinical trials evaluating the use of approved anti-androgens (bicalutamide, enzalutamide) in AR-positive TNBC has shown modest efficacy to date. In prostate cancer, bicalutamide binds to AR with low affinity and in the presence of AR gene amplification or mutation, can exhibit partial agonist activity leading to resistance. In order to increase affinity for AR and to avoid AR antagonist to agonist conversion synthesized 7-substituted umbelliferones (UMB) derivatives with a distinct scaffold modified from available AR antagonists (Kandil et al Bioorganic & Medicinal Chemistry Letters, 2016). These agents exhibited inhibitory activity in human prostate cancer cells lines at sub-micro molar level, a 50-fold and 30-fold improvement over bicalutamide and enzalutamide, respectively. We hypothesized that these novel AR antagonists would be effective in inhibiting the growth of AR-positive TNBC cells. Methods: TNBC AR negative mesenchymal MDA-MB-231 (as control) and AR positive MDA-MB-231 cells were utilized for determination of the efficacy of the UMB derivatives. For proliferation assays, viability of the cells was monitored over a period of 72 hours with redox dye Cell Titer-Blue. Standard Western blotting techniques were used for protein detection. For apoptosis analysis, standard flow cytometry reagents, FITC labelled Annexin V and Propidium Iodine(PI) mix were utilized. Results: UMB derivatives decreased the expression of AR in AR-positive MDA-MB-453 in a dose dependent manner. UMB derivatives, at micro Molar concentration decreased cell proliferation of AR-positive and interestingly AR-negative cell lines by 20 to 50%, also in a dose dependent manner. UMB derivatives induced apoptosis in both cell lines. Interestingly, UMB derivatives induced a change from a mesenchymal to epithelial phenotype in AR-negative MDA-MB-231 cells, which was confirmed by decreased expression of vimentin and other mesenchymal markers. Conclusions: Novel UMB derivatives inhibit growth and cause apoptosis in TNBC cells and induce mesenchymal-to-epithelial transition in an AR-negative mesenchymal TNBC cell line. Targeting AR with novel AR antagonists seem to be a promising therapeutic approach for AR-positive TNBC and further evaluation of AR antagonists in AR-negative mesenchymal TNBC is warranted. Citation Format: Saswati Bhattacharya, Yuanqi Cai, Steven Kurina, Pamela Westmark, Benjamin Hokanson, Matthew Anderson, Ruth O’Regan. Novel androgen receptor inhibitors in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1236. doi:10.1158/1538-7445.AM2017-1236

What is the mechanism of action of praziquantel and how might resistance strike?

Schistosomiasis, also known as bilharzia, is a neglected tropical disease affecting over 249 million people of which approximately 45% are school-aged children. Although there are significant numbers of people with the disease in Asia and South America, over 90% of those infected reside in Africa. The Global Burden of Disease Study 2010 estimated 11,700 deaths and 2,986,000 years lost to disability due to schistosomiasis in that year [1,2]. In 2012, the World Health Organization produced a ‘roadmap’ whose ultimate goal was the “...elimination of NTDs or reductions in their impacts to levels at which they are no longer considered public-health problems” [3]. Schistosomiasis was listed as a disease for potential elimination in the Eastern Mediterranean, Caribbean, Indonesia and Mekong River basin by 2015 and Brazil by 2020. Understandably, a more conservative note was sounded for Sub-Saharan Africa where worry over availability of medication was cited as the reason for failing to schedule elimination by 2020. The best-case scenario that could be made was with widespread availability of medication and strong political support schistosomiasis could be “...eliminated as a ‘public health problem’ in multiple countries in Africa by 2020.” The causative agents of schistosomiasis are digenetic trematode worms belonging the genus Schistosoma with Schistosoma mansoni, S. japonicum and S. haematobium being responsible for the majority of cases. Unfortunately, there is no vaccine available for the treatment of human schistosomiasis nor is the development of one on the horizon. Praziquantel (PZQ) is the only widely available drug for treatment of the disease and is thus at the heart of all control programs. It has been available for over 30 years yet the mechanism by which it kills schistosomes remains unknown and worries persist over the potential for mass administration campaigns to eventually diminish its usefulness. Here, we provide an introduction to schistosomiasis and discuss our current understanding of the mechanism of action of PZQ and the potential for widespread drug resistance.

Our Scope Expansion to Include Biologics

Chemical compounds with relatively low molecular weights, so-called small molecules in pharmaceutical parlance, have been the mainstay of drug-based therapeutics for many decades. More recently, large molecules, known as biologics, have received increasing attention and have become a large segment of drug research and development. Biologics have become an important segment of marketed drugs and are expected to expand further in the future. Most drug discovery and development organizations have shifted their business objectives over the past few years to emphasize protein-based therapeutic agents, such that they will become a greater proportion of their therapeutic pipelines. This transition, a dramatic shift from small-molecule drugs to high-value biopharmaceuticals, has powered a vibrant biotechnology expansion with the concomitant rise of many biopharma enterprises. ACS Medicinal Chemistry Letters recognizes this shift in the landscape of drug discovery and development, as well as the important contributions of medicinal chemists to the field of large-molecule therapeutics. Consequently, the journal is extending its welcome to medicinal chemistry-oriented manuscripts associated with molecular entities that are commonly referred to as “biologics”. Some examples include, but are not limited to, medicinal chemistry aspects of antibody–drug conjugates; protein therapeutics; and passive or active immunotherapies. The Editors encourage the submission of manuscripts pertaining to the identification, synthesis, optimization, and biological characterization of large bioactive molecules and drugs, as a complement to our long-standing emphasis on small molecular entities. As such, our advice to prospective authors has been modified accordingly in Instructions for Authors on our Web site.

Retraction of "novel 2-aminobenzamides as potential orally active antithrombotic agents".

[This retracts the article DOI: 10.1021/ml300217f.].

New Frontiers in Kinases: Second Generation Inhibitors-Going beyond Cancer.

It is a great pleasure to introduce the Special Issue “New Frontiers in Kinases: Second Generation Inhibitors”, which includes contributions from ACS Medicinal Chemistry Letters, Journal of Medicinal Chemistry, ACS Chemical Biology, and Biochemistry. The kinase area has been heavily studied with more than 500,000 published articles, the vast majority of which focus on cancer. We are now just beginning to unlock the potential of noncancer kinase targets. ACS Medicinal Chemistry Letters received an impressive number of high-quality submissions. Although it would go much beyond the scope of this editorial to comment in detail on all studies contained here, I would like to highlight a few representative studies that are very much in line with the theme and aims of this Issue: (a) Harrison et al. report on the “Discovery and Development of a Dual LIM-kinase and ROCK Inhibitor for the Treatment of Glaucoma”; (b) Rosse et al. present a Patent Highlight on “Novel Azaindazole Sulfonamides Inhibitors of Serum and Glucocorticoid Regulated Kinase”; (c) Thompson et al. in a Viewpoint speculate on the prospects for the development of Class II PI3K inhibitors; and (d) Goodwin et al. present an inhibitor mechanism study on the “Discovery of a Type III Inhibitor of LIM Kinase 2 that Binds in a DFG-out Conformation”. These representative studies provide a flavor of the diverse and exciting science in emerging areas assembled in this Special Issue. I would like to thank our authors for their many outstanding contributions. We also thank the numerous reviewers who, sometimes on rather short notice, diligently evaluated these manuscripts. Special thanks go to the Editors of ACS Medicinal Chemistry Letters and the editorial office staff for their continuous support of this project. Last but not least, we very much hope that the readers of ACS Medicinal Chemistry Letters will enjoy this Special Issue on New Frontiers on Kinases.

Evolution of the activity cliff concept for structure-activity relationship analysis and drug discovery.

Future Medicinal ChemistryVol. 6, No. 14 CommentaryEvolution of the activity cliff concept for structure–activity relationship analysis and drug discoveryJürgen BajorathJürgen BajorathSearch for more papers by this authorPublished Online:4 Nov 2014https://doi.org/10.4155/fmc.14.94AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: active compoundsactivity cliffscompound data mininglead optimizationmolecular similaritySAR analysisReferences1 Stumpfe D, Bajorath J. Exploring activity cliffs in medicinal chemistry. J. Med. Chem. 55(7), 2932–2942 (2012).Crossref, Medline, CAS, Google Scholar2 Stumpfe D, Hu Y, Dimova D, Bajorath J. Recent progress in understanding activity cliffs and their utility in medicinal chemistry. J. Med. Chem. 57(1), 18–28 (2014).Crossref, Medline, CAS, Google Scholar3 Hu Y, Bajorath J. Extending the activity cliff concept: structural categorization of activity cliffs and systematic identification of different types of cliffs in the ChEMBL database. J. Chem. Inf. Model 52(7), 1806–1811 (2012).Crossref, Medline, CAS, Google Scholar4 Griffen E, Leach AG, Robb GR, Warner DJ. Matched molecular pairs as a medicinal chemistry tool. J. Med. Chem. 54(22), 7739–7750 (2011).Crossref, Medline, CAS, Google Scholar5 Hu X, Hu Y, Vogt M, Stumpfe D, Bajorath, J. MMP-cliffs: systematic identification of activity cliffs on the basis of matched molecular pairs. J. Chem. Inf. Model 52(5), 1138–1145 (2012).Crossref, Medline, CAS, Google Scholar6 Hu Y, Stumpfe D, Bajorath J. Advancing the activity cliff concept [v1; ref status: indexed, http://f1000r.es/1wf] (2013). http://f1000research.com/articles/2-199/v1 Crossref, Google Scholar7 Gaulton A, Bellis LJ, Bento AP et al. ChEMBL: a large-scale bioactivity database for drug discovery Nucleic Acids Res. 40(Database issue), D1100–D1107 (2012).Crossref, Medline, CAS, Google Scholar8 Stumpfe D, Bajorath J. Frequency of occurrence and potency range distribution of activity cliffs in bioactive compounds. J. Chem. Inf. Model. 52(9), 2348–2353 (2012).Crossref, Medline, CAS, Google Scholar9 Stumpfe D, de la Vega de León A, Dimova D, Bajorath, J. Advancing the activity cliff concept, part II. [v1; ref status: indexed, http://f1000r.es/34p] (2014). http://f1000research.com/articles/3-75/v1 Crossref, Google Scholar10 Stumpfe D, Dimova D, Heikamp K, Bajorath J. Compound pathway model to capture SAR progression: comparison of activity cliff-dependent and -independent pathways. J. Chem. Inf. Model 53(5), 1067–1072 (2013).Crossref, Medline, CAS, Google Scholar11 Dimova D, Heikamp K, Stumpfe D Bajorath J. Do medicinal chemists learn from activity cliffs? A systematic evaluation of cliff progression in evolving compound data sets. J. Med. Chem. 56(8), 3339–3345 (2013).Crossref, Medline, CAS, Google Scholar12 Stumpfe D, Dimova D, Bajorath J. Composition and topology of activity cliff clusters formed by bioactive compounds. J. Chem. Inf. Model 54(2), 451–561 (2014).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByDrug target inference by mining transcriptional data using a novel graph convolutional network framework22 October 2021 | Protein & Cell, Vol. 13, No. 4Navigating into the Chemical Space of Monoamine Oxidase Inhibitors by Artificial Intelligence and Cheminformatics Approach1 September 2021 | ACS Omega, Vol. 6, No. 36Systematic Exploration of Activity Cliffs Containing Privileged Substructures24 January 2020 | Molecular Pharmaceutics, Vol. 17, No. 3Computational method for the identification of third generation activity cliffsMethodsX, Vol. 7Introducing a new category of activity cliffs with chemical modifications at multiple sites and rationalizing contributions of individual substitutionsBioorganic & Medicinal Chemistry, Vol. 27, No. 16Second-generation activity cliffs identified on the basis of target set-dependent potency difference criteriaHuabin Hu, Dagmar Stumpfe & Jürgen Bajorath19 March 2019 | Future Medicinal Chemistry, Vol. 11, No. 5Systematic identification of target set-dependent activity cliffsHuabin Hu, Dagmar Stumpfe & Jürgen Bajorath18 January 2019 | Future Science OA, Vol. 5, No. 27-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancerBioorganic & Medicinal Chemistry Letters, Vol. 26, No. 8Monitoring global growth of activity cliff information over time and assessing activity cliff frequencies and distributionsDagmar Stumpfe & Jürgen Bajorath27 August 2015 | Future Medicinal Chemistry, Vol. 7, No. 12 Vol. 6, No. 14 Follow us on social media for the latest updates Metrics Downloaded 120 times History Published online 4 November 2014 Published in print September 2014 Information© Future Science LtdKeywordsactive compoundsactivity cliffscompound data mininglead optimizationmolecular similaritySAR analysisFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Hybrid Porous Silicon- Rhodamine B Derivative Nanostructures as Chemical Sensor for Hg(II) Detection

In this work we propose a new method to produce a fluorescent chemical sensor for mercury detection (Hg(II)). This device is mainly based on the optical properties of porous silicon nanostructures (PSi) [1] coupled with the fluorescent properties of Rhodamine B [2] (Rh-urea-Ph-urea-Si) ligand derivative, which is covalently linked to PSi acting as receptor of metal ions. The Rh-urea-Ph-urea-Si (Ph=Phenil) compound was synthesized and its complexing ability was studied in liquid phase and solid by fluorescence spectrometry. The results showed that the fluorescence response of the metallic complex is metal concentration dependent. If the Hg(II) concentration increases, the florescence intensity also increases to reach the saturation point of the fluorophore. The electrochemical etching of crystalline silicon wafer [3] produced the PSi transducers, which in turn were functionalized with the organic receptors. The ligand infiltration into the PSi matrix and the metal coordination on the hybrid substrate were evaluated by specular reflectance, infrared and fluorescence spectroscopy, and SEM. Fluorescence microscopy confirmed the qualitative detection of Hg(II) ions due to the increase of the fluorescence observed after metal capture. The changes in electrical impedance upon porous silicon samples before and after the chemical modification, allowed us to obtain the approximate surface area of the porous devices. During the presentation of this work, the Hg (II) detection through voltammetric techniques will be discussed. Acknowledgements. This work was supported by the CONACYT, Project No. CB-153161 and 169634. P Mayela De la Cruz thanks the CONACYT Scholarship: 237466. We acknowledge to Olga Dávalos Montoya for FTIR support and Prof. Jaime Ruiz for the facilities provided for the use of the fluorescent microscope. References.[1] A. Melek, D. Wissem, M. Ghrib, C. Radhouane, Ezzaouia. Journal of Luminescence. 132 (2012) 277-281.[2] Zhisheng Wu, Xuanjun Wu, Yuhui Yang, Ting-bin Wen, Shoufa Han, Bioorganic & Medicinal Chemistry Letters. 22 (2012) 6358–6361.[3] G. Palestino, M. Martin, V. Agarwal, R. Legros, T. Cloitre, László Zimanyi, C. Gergely, Phys. Status Solidi C. 6(7) (2009) 1624-1628

A Special Thematic Compilation/Special Issue Crossover with Biochemistry, Journal of Medicinal Chemistry, and ACS Medicinal Chemistry Letters Focused on Kinases

ADVERTISEMENT RETURN TO ISSUEEditors LetterNEXTA Special Thematic Compilation/Special Issue Crossover with Biochemistry, Journal of Medicinal Chemistry, and ACS Medicinal Chemistry Letters Focused on KinasesDaniel RauhCite this: ACS Chem. Biol. 2014, 9, 3, 579–580Publication Date (Web):March 21, 2014Publication History Published online21 March 2014Published inissue 21 March 2014https://doi.org/10.1021/cb500150dCopyright © 2014 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views728Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (127 KB) Get e-AlertsSUBJECTS:Cancer,Inhibitors,Kinase inhibitors,Medicinal chemistry,Peptides and proteins Get e-Alerts

Evolving therapies for the treatment of HCV viral hepatitis.

Evolving therapies for the treatment of HCV viral hepatitis.

Call for Papers! A Special Thematic Compilation/Special Issue Crossover with ACS Chemical Biology, ACS Medicinal Chemistry Letters, and the Journal of Medicinal Chemistry Focused on New Frontiers in Kinases

Call for Papers! A Special Thematic Compilation/Special Issue Crossover with <i>ACS Chemical Biology, ACS Medicinal Chemistry Letters</i>, and the <i>Journal of Medicinal Chemistry</i> Focused on New Frontiers in Kinases

New frontiers in kinases: special issue.

Human protein kinases (PKs) represent the third largest enzyme class and are responsible for modifying an estimated one-third of the human proteome.1 These enzymes catalyze the transfer of the gamma phosphate group from ATP to specific serine, threonine, or tyrosine hydroxyl groups on a target protein substrate, involved in a number of cell signaling pathways. It has been firmly demonstrated that kinase alterations (especially hyperactivation, hyperproduction, or mutations), leading to the disruption of cell signaling cascades, play important roles in several diseases, including cancer, inflammation, neurological disorders, and diabetes, thus making PKs one of the most attractive targets for pharmaceutical industry.2 Discovery of kinase inhibitors has been successful, with about 150 kinase-targeted drugs in clinical development and more than 20 drugs approved by the Food and Drug Administration (FDA) for treatment of tumors. Many of these drugs are multitargeted inhibitors since they inhibit more than one kinase, and this activity is important in many malignancies, where several cell pathways are deregulated. Despite the increasing number of FDA-approved kinase drugs, the identification of selective molecules continued to be a great challenge.3 Indeed, almost all kinase inhibitors studied so far bind the ATP binding pocket, and the research of compounds with allosteric mechanisms of inhibition is at an early stage.4 Although oncology will be still for a long time the main focus of kinase drug discovery, the development of kinase inhibitors to treat diseases other than cancer is increasing. Many human pathologies including chronic inflammatory and autoimmune diseases, diabetes, infectious diseases, cardiovascular disorders, neurodegenerative diseases, and even AIDS are the therapeutic areas on which the kinase drug discovery programs are focusing. Identifying novel kinases, obtaining target selectivity, developing allosteric inhibitors, applying kinase inhibitors to nononcology therapeutic areas, overcoming drug resistance and undesired side effects, finding efficient screening and profiling technologies, and exploring novel applications for existing inhibitors are only some of the most important challenges to be faced by researchers over the next 10 years.5 Because of the continued increasing interest in the kinase drug discovery, the collection of the major advancements in the field has become one of the main objectives of ACS Medicinal Chemistry Letters, Journal of Medicinal Chemistry, ACS Chemical Biology, and Biochemistry, which will collaborate to publish a thematic collection on kinases in January 2015. We hope that these Special Issues will stimulate the discussion on the most important recent findings and will favor the progress in this area. We encourage you to submit your manuscripts at https://acs.manuscriptcentral.com/acs by September 1, 2014. Accepted articles for the thematic issues can be published immediately as JAMS and/or ASAPs but will be published together in the January 2015 Special Issue. In addition, articles will appear on a special online landing page dedicated to kinases drug discovery.