Pub Date : 2022-06-01Epub Date: 2022-07-19DOI: 10.4155/fdd-2022-0007
Birgit Caspar, Pietro Cocchiara, Armelle Melet, Kristof Van Emelen, Annegret Van der Aa, Graeme Milligan, Jean-Philippe Herbeuval
CXCR4 has been a target of interest in drug discovery for numerous years. However, so far, most if not all studies focused on finding antagonists of CXCR4 function. Recent studies demonstrate that targeting a minor allosteric pocket of CXCR4 induces an immunomodulating effect in immune cells expressing CXCR4, connected to the TLR pathway. Compounds binding in this minor pocket seem to be functionally selective with inverse agonistic properties in selected GPCR signaling pathways (Gi activation), but additional signaling pathways are likely to be involved in the immunomodulating effects. In depth research into these CXCR4-targeted immunomodulators could lead to novel treatment options for (auto)-immune diseases.
{"title":"CXCR4 as a novel target in immunology: moving away from typical antagonists.","authors":"Birgit Caspar, Pietro Cocchiara, Armelle Melet, Kristof Van Emelen, Annegret Van der Aa, Graeme Milligan, Jean-Philippe Herbeuval","doi":"10.4155/fdd-2022-0007","DOIUrl":"10.4155/fdd-2022-0007","url":null,"abstract":"<p><p>CXCR4 has been a target of interest in drug discovery for numerous years. However, so far, most if not all studies focused on finding antagonists of CXCR4 function. Recent studies demonstrate that targeting a minor allosteric pocket of CXCR4 induces an immunomodulating effect in immune cells expressing CXCR4, connected to the TLR pathway. Compounds binding in this minor pocket seem to be functionally selective with inverse agonistic properties in selected GPCR signaling pathways (G<sub>i</sub> activation), but additional signaling pathways are likely to be involved in the immunomodulating effects. In depth research into these CXCR4-targeted immunomodulators could lead to novel treatment options for (auto)-immune diseases.</p>","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":"4 2","pages":"FDD77"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/b8/fdd-04-77.PMC9298491.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The possible drug for cancer and metastasis prevention","authors":"V. Pak","doi":"10.4155/fdd-2022-0008","DOIUrl":"https://doi.org/10.4155/fdd-2022-0008","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42431723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The standard drug discovery paradigm of single molecule – single biological target – single biological effect is perhaps particularly unsuitable for anti-infective drug discovery. This is due to the rapid evolution of resistance likely to be observed with single target drugs. Multitargeted anti-infective drugs are likely to be superior due to their lower susceptibility to target-related resistance mechanisms. Strathclyde minor groove binders are a class of compounds which have been developed by adopting the multitargeted anti-infective drugs paradigm, and their effectiveness against a wide range of pathogenic organisms is discussed. The renaming of this class to Strathclyde nucleic acid binders is also presented due to their likely targets including both DNA and RNA.
{"title":"Multitargeted anti-infective drugs: resilience to resistance in the antimicrobial resistance era","authors":"C. Suckling, I. Hunter, Fraser J. Scott","doi":"10.4155/fdd-2022-0001","DOIUrl":"https://doi.org/10.4155/fdd-2022-0001","url":null,"abstract":"The standard drug discovery paradigm of single molecule – single biological target – single biological effect is perhaps particularly unsuitable for anti-infective drug discovery. This is due to the rapid evolution of resistance likely to be observed with single target drugs. Multitargeted anti-infective drugs are likely to be superior due to their lower susceptibility to target-related resistance mechanisms. Strathclyde minor groove binders are a class of compounds which have been developed by adopting the multitargeted anti-infective drugs paradigm, and their effectiveness against a wide range of pathogenic organisms is discussed. The renaming of this class to Strathclyde nucleic acid binders is also presented due to their likely targets including both DNA and RNA.","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42437797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Welcome to Volume 4 of Future Drug Discovery","authors":"H. Wall","doi":"10.4155/fdd-2022-0006","DOIUrl":"https://doi.org/10.4155/fdd-2022-0006","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47682253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The use of psychedelics as medicines and for overall better brain health is potentially one of the most transformative developments given their immediate and long-lasting therapeutic effects across a plethora of neuropsychiatric disorders and, more recently, some neurodegenerative diseases. The US psychedelic drugs market is forecasted to grow by 16.3% by 2027 due to the increasing prevalence of treatment-resistant depression and mental health disorders. Decades-long restrictions, which date back to when psychedelics were declared controlled substances in 1970, have been lifted to allow researchers to publish on the therapeutic benefits of psychedelics. This review will feature the incredible depth of research underway revealing how psychedelics impact brain structure and function to treat mental health and other neurological disorders.
{"title":"The promise of psychedelic research","authors":"Carina S Peritore","doi":"10.4155/fdd-2021-0012","DOIUrl":"https://doi.org/10.4155/fdd-2021-0012","url":null,"abstract":"The use of psychedelics as medicines and for overall better brain health is potentially one of the most transformative developments given their immediate and long-lasting therapeutic effects across a plethora of neuropsychiatric disorders and, more recently, some neurodegenerative diseases. The US psychedelic drugs market is forecasted to grow by 16.3% by 2027 due to the increasing prevalence of treatment-resistant depression and mental health disorders. Decades-long restrictions, which date back to when psychedelics were declared controlled substances in 1970, have been lifted to allow researchers to publish on the therapeutic benefits of psychedelics. This review will feature the incredible depth of research underway revealing how psychedelics impact brain structure and function to treat mental health and other neurological disorders.","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45818816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interview with Hunterian CEO Dr Vinod Jaskula-Ranga","authors":"Vinod Jaskula-Ranga","doi":"10.4155/fdd-2021-0011","DOIUrl":"https://doi.org/10.4155/fdd-2021-0011","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48740374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabrielle Brewer, Anne-Marie Fortier, Morag Park, Christopher Moraes
Although cancer-associated fibroblasts (CAFs) have gained increased attention for supporting cancer progression, current CAF-targeted therapeutic options are limited and failing in clinical trials. As the largest component of the tumor microenvironment (TME), CAFs alter the biochemical and physical structure of the TME, modulating cancer progression. Here, we review the role of CAFs in altering drug response, modifying the TME mechanics and the current models for studying CAFs. To provide new perspectives, we highlight key considerations of CAF activity and discuss emerging technologies that can better address CAFs; and therefore, increase the likelihood of therapeutic efficacy. We argue that CAFs are crucial components of the cancer drug discovery pipeline and incorporating these cells will improve drug discovery success rates.
{"title":"The case for cancer-associated fibroblasts: essential elements in cancer drug discovery?","authors":"Gabrielle Brewer, Anne-Marie Fortier, Morag Park, Christopher Moraes","doi":"10.4155/fdd-2021-0004","DOIUrl":"https://doi.org/10.4155/fdd-2021-0004","url":null,"abstract":"<p><p>Although cancer-associated fibroblasts (CAFs) have gained increased attention for supporting cancer progression, current CAF-targeted therapeutic options are limited and failing in clinical trials. As the largest component of the tumor microenvironment (TME), CAFs alter the biochemical and physical structure of the TME, modulating cancer progression. Here, we review the role of CAFs in altering drug response, modifying the TME mechanics and the current models for studying CAFs. To provide new perspectives, we highlight key considerations of CAF activity and discuss emerging technologies that can better address CAFs; and therefore, increase the likelihood of therapeutic efficacy. We argue that CAFs are crucial components of the cancer drug discovery pipeline and incorporating these cells will improve drug discovery success rates.</p>","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":"4 1","pages":"FDD71"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/c6/fdd-04-71.PMC9112234.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eswara Naga Hanuma Kumar Ghali, Vijian Dhevan, Shravan K Narmala, Meena Jaggi, Subhash C Chauhan, Murali M Yallapu
Eswara Naga Hanuma Kumar Ghali1,2, Vijian Dhevan3, Shravan K Narmala4, Meena Jaggi1,2, Subhash C Chauhan1,2 & Murali M Yallapu*,1,2 1Department of Immunology & Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA 2South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA 3Department of Surgery, University of Texas Rio Grande Valley, Harlingen, TX 78550, USA 4DHR Health Hematology Oncology Institute, DHR Health, Edinburg, TX 78539, USA *Author for correspondence: Tel.: +956 296 1734; murali.yallapu@utrgv.edu
{"title":"Breakthrough medicines during the COVID-19 pandemic era.","authors":"Eswara Naga Hanuma Kumar Ghali, Vijian Dhevan, Shravan K Narmala, Meena Jaggi, Subhash C Chauhan, Murali M Yallapu","doi":"10.4155/fdd-2022-0002","DOIUrl":"https://doi.org/10.4155/fdd-2022-0002","url":null,"abstract":"Eswara Naga Hanuma Kumar Ghali1,2, Vijian Dhevan3, Shravan K Narmala4, Meena Jaggi1,2, Subhash C Chauhan1,2 & Murali M Yallapu*,1,2 1Department of Immunology & Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA 2South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA 3Department of Surgery, University of Texas Rio Grande Valley, Harlingen, TX 78550, USA 4DHR Health Hematology Oncology Institute, DHR Health, Edinburg, TX 78539, USA *Author for correspondence: Tel.: +956 296 1734; murali.yallapu@utrgv.edu","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":"4 1","pages":"FDD69"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/4b/fdd-04-69.PMC8842712.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9730310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kinetic intracellular assay measures compound binding kinetics at intracellular targets within living cells","authors":"Charles S Lay, Daniel A. Thomas, P. Craggs","doi":"10.4155/fdd-2021-0010","DOIUrl":"https://doi.org/10.4155/fdd-2021-0010","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43935920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Banegas-Luna, Miguel Carmena-Bargueño, H. Pérez‐Sánchez
{"title":"Quo vadis artificial intelligence and personalized medicine?","authors":"A. Banegas-Luna, Miguel Carmena-Bargueño, H. Pérez‐Sánchez","doi":"10.4155/fdd-2021-0009","DOIUrl":"https://doi.org/10.4155/fdd-2021-0009","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44664356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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