The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents

The main difficulty in the development of ATP antagonist kinase inhibitors is target specificity, since the ATP-binding motif is present in many proteins. We introduce a strategy that has allowed us to identify compounds from a kinase inhibitor library that block the cyclin-dependent kinases responsible for regulating transcription, i.e., CDK7 and especially CDK9. The screening cascade employs cellular phenotypic assays based on mitotic index and nuclear p53 protein accumulation. This permitted us to classify compounds into transcriptional, cell cycle, and mitotic inhibitor groups. We describe the characterization of the transcriptional inhibitor class in terms of kinase inhibition profile, cellular mode of action, and selectivity for transformed cells. A structural selectivity rationale was used to optimize potency and biopharmaceutical properties and led to the development of a transcriptional inhibitor, 3,4-dimethyl-5-[2-(4-piperazin-1-yl-phenylamino)-pyrimidin-4-yl]-3H- thiazol-2-one, with anticancer activity in animal models. © 2010 Elsevier Ltd All rights reserved

Problems in Cross-Cultural Use of the Hospital Anxiety and Depression Scale:"No Butterflies in the Desert"

<p>Objective: The Hospital Anxiety and Depression Scale (HADS) is widely used to screen for anxiety and depression. A large literature is citable in support of its validity, but difficulties are increasingly being identified, such as inexplicably discrepant optimal cutpoints and inconsistent factor-structures. This article examines whether these problems could be due to the construction of the HADS that poses difficulties for translation and cross-cultural use.</p><p>Methods: Authors' awareness of difficulties translating the HADS were identified by examining 20% of studies using the HADS, obtained by a systematic literature search in Pubmed and PsycINFO in May 2012. Reports of use of translations and validation studies were recorded for papers from non-English speaking countries. Narrative and systematic reviews were examined for how authors dealt with different translations.</p><p>Results: Of 417 papers from non-English speaking countries, only 45% indicated whether a translation was used. Studies validating translations were cited in 54%. Seventeen reviews, incorporating data from diverse translated versions, were examined. Only seven mentioned issues of language and culture, and none indicated insurmountable problems in integrating results from different translations.</p><p>Conclusion: Initial decisions concerning item content and response options likely leave the HADS difficult to translate, but we failed to find an acknowledgment of problems in articles involving its translation and cross-cultural use. Investigators' lack of awareness of these issues can lead to anomalous results and difficulties in interpretation and integration of these results. Reviews tend to overlook these issues and most reviews indiscriminately integrate results from studies performed in different countries. Cross-culturally valid, but literally translated versions of the HADS may not be attainable, and specific cutpoints may not be valid across cultures and language. Claims about rates of anxiety and depression based on integrating cross-cultural data or using the same cutpoint across languages and culture should be subject to critical scrutiny.</p>