Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Drug Discov Today. 2023 Dec 26:103865. doi: 10.1016/j.drudis.2023.103865. Online ahead of print.ABSTRACTPROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportuni...
Source: Drug Discovery Today - December 28, 2023 Category: Drugs & Pharmacology Authors: Wenzhan Yang Sugandha Saboo Liping Zhou Sean Askin Annette Bak Source Type: research
Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Drug Discov Today. 2023 Dec 26:103865. doi: 10.1016/j.drudis.2023.103865. Online ahead of print.ABSTRACTPROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportuni...
Source: Drug Discovery Today - December 28, 2023 Category: Drugs & Pharmacology Authors: Wenzhan Yang Sugandha Saboo Liping Zhou Sean Askin Annette Bak Source Type: research
Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Drug Discov Today. 2023 Dec 26:103865. doi: 10.1016/j.drudis.2023.103865. Online ahead of print.ABSTRACTPROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportuni...
Source: Drug Discovery Today - December 28, 2023 Category: Drugs & Pharmacology Authors: Wenzhan Yang Sugandha Saboo Liping Zhou Sean Askin Annette Bak Source Type: research
Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Drug Discov Today. 2023 Dec 26:103865. doi: 10.1016/j.drudis.2023.103865. Online ahead of print.ABSTRACTPROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportuni...
Source: Drug Discovery Today - December 28, 2023 Category: Drugs & Pharmacology Authors: Wenzhan Yang Sugandha Saboo Liping Zhou Sean Askin Annette Bak Source Type: research
Increased contribution of small companies to late-entry drugs: a changing trend in FDA-approved drugs during the 2020s
Drug Discov Today. 2023 Dec 23:103866. doi: 10.1016/j.drudis.2023.103866. Online ahead of print.ABSTRACTSmall- and medium-sized enterprises (SMEs) have significantly boosted innovative drug discovery, whereas large pharmaceutical companies have focused on incremental drug innovation. I explored the evolving role of SMEs in late-entry drug discovery. A comparative analysis of new drugs approved by the US Food and Drug Administration (FDA) during the 2020s with those approved previously revealed that SMEs have expanded their role to late-entry drug discovery while maintaining their contribution to first-in-target drug discov...
Source: Drug Discovery Today - December 25, 2023 Category: Drugs & Pharmacology Authors: Ryo Okuyama Source Type: research
Increased contribution of small companies to late-entry drugs: a changing trend in FDA-approved drugs during the 2020s
Drug Discov Today. 2023 Dec 23:103866. doi: 10.1016/j.drudis.2023.103866. Online ahead of print.ABSTRACTSmall- and medium-sized enterprises (SMEs) have significantly boosted innovative drug discovery, whereas large pharmaceutical companies have focused on incremental drug innovation. I explored the evolving role of SMEs in late-entry drug discovery. A comparative analysis of new drugs approved by the US Food and Drug Administration (FDA) during the 2020s with those approved previously revealed that SMEs have expanded their role to late-entry drug discovery while maintaining their contribution to first-in-target drug discov...
Source: Drug Discovery Today - December 25, 2023 Category: Drugs & Pharmacology Authors: Ryo Okuyama Source Type: research
Increased contribution of small companies to late-entry drugs: a changing trend in FDA-approved drugs during the 2020s
Drug Discov Today. 2023 Dec 23:103866. doi: 10.1016/j.drudis.2023.103866. Online ahead of print.ABSTRACTSmall- and medium-sized enterprises (SMEs) have significantly boosted innovative drug discovery, whereas large pharmaceutical companies have focused on incremental drug innovation. I explored the evolving role of SMEs in late-entry drug discovery. A comparative analysis of new drugs approved by the US Food and Drug Administration (FDA) during the 2020s with those approved previously revealed that SMEs have expanded their role to late-entry drug discovery while maintaining their contribution to first-in-target drug discov...
Source: Drug Discovery Today - December 25, 2023 Category: Drugs & Pharmacology Authors: Ryo Okuyama Source Type: research
Recent advances in dual-drug co-amorphous systems
Drug Discov Today. 2023 Dec 21:103863. doi: 10.1016/j.drudis.2023.103863. Online ahead of print.ABSTRACTPoor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including improvements in formulation, manufacturing, and solid-state characterization, and highlights the importance of enhancing sol...
Source: Drug Discovery Today - December 23, 2023 Category: Drugs & Pharmacology Authors: Rutuja Shelke Varalakshmi Velagacherla Usha Yogendra Nayak Source Type: research
Mapping the evolution of inhaled drug delivery research: Trends, collaborations, and emerging frontiers
Drug Discov Today. 2023 Dec 21:103864. doi: 10.1016/j.drudis.2023.103864. Online ahead of print.ABSTRACTInhaled drug delivery is a unique administration route known for its ability to directly target pulmonary or brain regions, facilitating rapid onset and circumventing the hepatic first-pass effect. To characterize current global trends and provide a visual overview of the latest trends in inhaled drug delivery research, bibliometric analysis of data acquired from the Web of Science Core Collection database was performed via VOSviewer and CiteSpace. Inhaled drug delivery can not only be utilized in respiratory diseases bu...
Source: Drug Discovery Today - December 23, 2023 Category: Drugs & Pharmacology Authors: Xinyuan Li Zhengxing Su Chunyou Wang Wen Wu Yan Zhang Chenhui Wang Source Type: research
Recent advances in dual-drug co-amorphous systems
Drug Discov Today. 2023 Dec 21:103863. doi: 10.1016/j.drudis.2023.103863. Online ahead of print.ABSTRACTPoor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including improvements in formulation, manufacturing, and solid-state characterization, and highlights the importance of enhancing sol...
Source: Drug Discovery Today - December 23, 2023 Category: Drugs & Pharmacology Authors: Rutuja Shelke Varalakshmi Velagacherla Usha Yogendra Nayak Source Type: research
Mapping the evolution of inhaled drug delivery research: Trends, collaborations, and emerging frontiers
Drug Discov Today. 2023 Dec 21:103864. doi: 10.1016/j.drudis.2023.103864. Online ahead of print.ABSTRACTInhaled drug delivery is a unique administration route known for its ability to directly target pulmonary or brain regions, facilitating rapid onset and circumventing the hepatic first-pass effect. To characterize current global trends and provide a visual overview of the latest trends in inhaled drug delivery research, bibliometric analysis of data acquired from the Web of Science Core Collection database was performed via VOSviewer and CiteSpace. Inhaled drug delivery can not only be utilized in respiratory diseases bu...
Source: Drug Discovery Today - December 23, 2023 Category: Drugs & Pharmacology Authors: Xinyuan Li Zhengxing Su Chunyou Wang Wen Wu Yan Zhang Chenhui Wang Source Type: research
Human carnosinases: A brief history, medicinal relevance, and in silico analyses
Drug Discov Today. 2023 Dec 19:103860. doi: 10.1016/j.drudis.2023.103860. Online ahead of print.ABSTRACTCarnosine, an endogenous dipeptide, has been found to have a plethora of medicinal properties, such as antioxidant, antiageing, and chelating effects, but with one downside: a short half-life. Carnosinases and two hydrolytic enzymes, which remain enigmatic, are responsible for these properties. Hence, here we emphasize why research is valuable for better understanding crucial concepts like ageing, neurodegradation, and cancerogenesis, given that inhibition of carnosinases might significantly prolong carnosine bioavailabi...
Source: Drug Discovery Today - December 21, 2023 Category: Drugs & Pharmacology Authors: Klaudia Chmielewska Serena Vittorio Silvia Gervasoni Krystyna Dzierzbicka Iwona Inkielewicz-Stepniak Giulio Vistoli Source Type: research
Human carnosinases: A brief history, medicinal relevance, and in silico analyses
Drug Discov Today. 2023 Dec 19:103860. doi: 10.1016/j.drudis.2023.103860. Online ahead of print.ABSTRACTCarnosine, an endogenous dipeptide, has been found to have a plethora of medicinal properties, such as antioxidant, antiageing, and chelating effects, but with one downside: a short half-life. Carnosinases and two hydrolytic enzymes, which remain enigmatic, are responsible for these properties. Hence, here we emphasize why research is valuable for better understanding crucial concepts like ageing, neurodegradation, and cancerogenesis, given that inhibition of carnosinases might significantly prolong carnosine bioavailabi...
Source: Drug Discovery Today - December 21, 2023 Category: Drugs & Pharmacology Authors: Klaudia Chmielewska Serena Vittorio Silvia Gervasoni Krystyna Dzierzbicka Iwona Inkielewicz-Stepniak Giulio Vistoli Source Type: research
Mechanisms and prospects of piezoelectric materials as smart delivery vehicles in cancer treatment
Drug Discov Today. 2023 Dec 18:103862. doi: 10.1016/j.drudis.2023.103862. Online ahead of print.ABSTRACTPiezoelectric materials, capable of converting mechanical energy into electrical energy and vice versa, have emerged as promising candidates for designing intelligent drug delivery vehicles. Leveraging their inherent electrical properties, these materials respond to external stimuli, such as mechanical forces and electrical signals, to control drug release. By integrating piezoelectric materials into drug delivery systems, we can achieve exacting control over drug-release mechanisms. Piezoelectric materials hold enormous...
Source: Drug Discovery Today - December 20, 2023 Category: Drugs & Pharmacology Authors: Haleema Fayaz Tanishka Gupta Safia Obaidur Rab Saurabh Kumar Jha Sandeep Kumar Source Type: research
GPR39: an orphan receptor begging for ligands
Drug Discov Today. 2023 Dec 18:103861. doi: 10.1016/j.drudis.2023.103861. Online ahead of print.ABSTRACTProgress in the understanding the receptor GPR39 is held up by inconsistent pharmacological data. First, the endogenous ligand(s) remain(s) contentious. Data pointing to zinc ions (Zn2+) and/or eicosanoids as endogenous ligands are a matter of debate. Second, there are uncertainties in the specificity of the widely used synthetic ligand (agonist) TC-G 1008. Third, activation of GPR39 has been often proposed as a novel treatment strategy, but new data also support that inhibition might be beneficial in certain disease con...
Source: Drug Discovery Today - December 20, 2023 Category: Drugs & Pharmacology Authors: Urszula Doboszewska Wolfgang Maret Piotr Wla ΕΊ Source Type: research
