Molecular medicinal insights into scaffold hopping-based drug discovery success
Drug Discov Today. 2023 Nov 25:103845. doi: 10.1016/j.drudis.2023.103845. Online ahead of print.ABSTRACTIn both academia and the pharmaceutical industry, innovative hypotheses, methodologies and technologies that can shorten the drug research and development, leading to higher success rates, are vital In this review, we demonstrate how innovative variations of the scaffold-hopping strategy have been used to create new druggable molecular spaces, drugs, clinical candidates, preclinical candidates, and bioactive agents. We also analyze molecular modulations that enabled improvements of the pharmacodynamic (PD), physiochemica...
Source: Drug Discovery Today - November 28, 2023 Category: Drugs & Pharmacology Authors: Ayan Acharya Mukul Yadav Mithilesh Nagpure Sanathanalaxmi Kumarsan Sankar K Guchhait Source Type: research
Molecular medicinal insights into scaffold hopping-based drug discovery success
Drug Discov Today. 2023 Nov 25:103845. doi: 10.1016/j.drudis.2023.103845. Online ahead of print.ABSTRACTIn both academia and the pharmaceutical industry, innovative hypotheses, methodologies and technologies that can shorten the drug research and development, leading to higher success rates, are vital In this review, we demonstrate how innovative variations of the scaffold-hopping strategy have been used to create new druggable molecular spaces, drugs, clinical candidates, preclinical candidates, and bioactive agents. We also analyze molecular modulations that enabled improvements of the pharmacodynamic (PD), physiochemica...
Source: Drug Discovery Today - November 28, 2023 Category: Drugs & Pharmacology Authors: Ayan Acharya Mukul Yadav Mithilesh Nagpure Sanathanalaxmi Kumarsan Sankar K Guchhait Source Type: research
Valorization of biomass polyphenols as potential tyrosinase inhibitors
Drug Discov Today. 2023 Nov 22:103843. doi: 10.1016/j.drudis.2023.103843. Online ahead of print.ABSTRACTTyrosinases (TYRs; EC 1.14.18.1) catalyze two sequential oxidative reactions of the melanin biosynthesis pathway and play an important role in mammalian pigmentation and enzymatic browning of fruit and vegetables. Inhibition of TYR activity is therefore an attractive target for new drugs and/or food ingredients. In addition, increasing evidence suggests that TYR regulation could be a novel target for treatments of cancer and Parkinson's disease. Biomasses, notably industrial byproducts and biowaste, are good sustainable ...
Source: Drug Discovery Today - November 24, 2023 Category: Drugs & Pharmacology Authors: Thanh-Nhat Pham Elisabeth A Cazier Emmanuelle Gormally Philip Lawrence Source Type: research
Systematic review and QSPR analysis of chemical penetration through the nail to inform onychomycosis candidate selection
Drug Discov Today. 2023 Nov 22:103844. doi: 10.1016/j.drudis.2023.103844. Online ahead of print.ABSTRACTRecalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred. Interestingly, chemical polarity had li...
Source: Drug Discovery Today - November 24, 2023 Category: Drugs & Pharmacology Authors: Osamah S Malallah Lucy Coleman Sara M Nasereddin Mohammad Lockhat Tao Chen Stuart A Jones Source Type: research
Valorization of biomass polyphenols as potential tyrosinase inhibitors
Drug Discov Today. 2023 Nov 22:103843. doi: 10.1016/j.drudis.2023.103843. Online ahead of print.ABSTRACTTyrosinases (TYRs; EC 1.14.18.1) catalyze two sequential oxidative reactions of the melanin biosynthesis pathway and play an important role in mammalian pigmentation and enzymatic browning of fruit and vegetables. Inhibition of TYR activity is therefore an attractive target for new drugs and/or food ingredients. In addition, increasing evidence suggests that TYR regulation could be a novel target for treatments of cancer and Parkinson's disease. Biomasses, notably industrial byproducts and biowaste, are good sustainable ...
Source: Drug Discovery Today - November 24, 2023 Category: Drugs & Pharmacology Authors: Thanh-Nhat Pham Elisabeth A Cazier Emmanuelle Gormally Philip Lawrence Source Type: research
Systematic review and QSPR analysis of chemical penetration through the nail to inform onychomycosis candidate selection
Drug Discov Today. 2023 Nov 22:103844. doi: 10.1016/j.drudis.2023.103844. Online ahead of print.ABSTRACTRecalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred. Interestingly, chemical polarity had li...
Source: Drug Discovery Today - November 24, 2023 Category: Drugs & Pharmacology Authors: Osamah S Malallah Lucy Coleman Sara M Nasereddin Mohammad Lockhat Tao Chen Stuart A Jones Source Type: research
Ligands and receptors in human cytomegalovirus entry: current therapies and new directions
Drug Discov Today. 2023 Nov 20:103833. doi: 10.1016/j.drudis.2023.103833. Online ahead of print.ABSTRACTThe demand for human cytomegalovirus (HCMV) vaccines was first raised by a committee convened during the 1990s. A comprehensive investigation into the mechanism of viral infection supports the prioritization of developing drugs or vaccines that specifically target receptors and ligands involved in the infection process. As primary targets for neutralizing antibodies to combat HCMV, viral ligands (trimer, pentamer, and glycoprotein B) have crucial roles and exhibit substantial antiviral potential, which could be exploited...
Source: Drug Discovery Today - November 22, 2023 Category: Drugs & Pharmacology Authors: Min Zhang Xiaochen Wang Jianshe Li Fujun Peng Zhijun Liu Zhe-Sheng Chen Source Type: research
Ligands and receptors in human cytomegalovirus entry: current therapies and new directions
Drug Discov Today. 2023 Nov 20:103833. doi: 10.1016/j.drudis.2023.103833. Online ahead of print.ABSTRACTThe demand for human cytomegalovirus (HCMV) vaccines was first raised by a committee convened during the 1990s. A comprehensive investigation into the mechanism of viral infection supports the prioritization of developing drugs or vaccines that specifically target receptors and ligands involved in the infection process. As primary targets for neutralizing antibodies to combat HCMV, viral ligands (trimer, pentamer, and glycoprotein B) have crucial roles and exhibit substantial antiviral potential, which could be exploited...
Source: Drug Discovery Today - November 22, 2023 Category: Drugs & Pharmacology Authors: Min Zhang Xiaochen Wang Jianshe Li Fujun Peng Zhijun Liu Zhe-Sheng Chen Source Type: research
Ligands and receptors in human cytomegalovirus entry: current therapies and new directions
Drug Discov Today. 2023 Nov 20:103833. doi: 10.1016/j.drudis.2023.103833. Online ahead of print.ABSTRACTThe demand for human cytomegalovirus (HCMV) vaccines was first raised by a committee convened during the 1990s. A comprehensive investigation into the mechanism of viral infection supports the prioritization of developing drugs or vaccines that specifically target receptors and ligands involved in the infection process. As primary targets for neutralizing antibodies to combat HCMV, viral ligands (trimer, pentamer, and glycoprotein B) have crucial roles and exhibit substantial antiviral potential, which could be exploited...
Source: Drug Discovery Today - November 22, 2023 Category: Drugs & Pharmacology Authors: Min Zhang Xiaochen Wang Jianshe Li Fujun Peng Zhijun Liu Zhe-Sheng Chen Source Type: research
Targeting SARS-CoV-2 nonstructural protein 3: function, structure, inhibition, and perspective in drug discovery
Drug Discov Today. 2023 Nov 15:103832. doi: 10.1016/j.drudis.2023.103832. Online ahead of print.ABSTRACTAs a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus...
Source: Drug Discovery Today - November 17, 2023 Category: Drugs & Pharmacology Authors: Xin Li Yongcheng Song Source Type: research
Targeting SARS-CoV-2 nonstructural protein 3: function, structure, inhibition, and perspective in drug discovery
Drug Discov Today. 2023 Nov 15:103832. doi: 10.1016/j.drudis.2023.103832. Online ahead of print.ABSTRACTAs a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus...
Source: Drug Discovery Today - November 17, 2023 Category: Drugs & Pharmacology Authors: Xin Li Yongcheng Song Source Type: research
Targeting SARS-CoV-2 nonstructural protein 3: function, structure, inhibition, and perspective in drug discovery
Drug Discov Today. 2023 Nov 15:103832. doi: 10.1016/j.drudis.2023.103832. Online ahead of print.ABSTRACTAs a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus...
Source: Drug Discovery Today - November 17, 2023 Category: Drugs & Pharmacology Authors: Xin Li Yongcheng Song Source Type: research
Targeting SARS-CoV-2 nonstructural protein 3: function, structure, inhibition, and perspective in drug discovery
Drug Discov Today. 2023 Nov 15:103832. doi: 10.1016/j.drudis.2023.103832. Online ahead of print.ABSTRACTAs a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus...
Source: Drug Discovery Today - November 17, 2023 Category: Drugs & Pharmacology Authors: Xin Li Yongcheng Song Source Type: research
Multiorgan locked-state model of chronic diseases and systems pharmacology opportunities
Drug Discov Today. 2023 Nov 13:103825. doi: 10.1016/j.drudis.2023.103825. Online ahead of print.ABSTRACTWith increasing human life expectancy, the global medical burden of chronic diseases is growing. Hence, chronic diseases are a pressing health concern and will continue to be in decades to come. Chronic diseases often involve multiple malfunctioning organs in the body. An imminent question is how interorgan crosstalk contributes to the etiology of chronic diseases. We conceived the locked-state model (LoSM), which illustrates how interorgan communication can give rise to body-wide memory-like properties that 'lock' healt...
Source: Drug Discovery Today - November 15, 2023 Category: Drugs & Pharmacology Authors: Choong Yong Ung Cristina Correia Hu Li Christopher M Adams Jennifer J Westendorf Shizhen Zhu Source Type: research
Multiorgan locked-state model of chronic diseases and systems pharmacology opportunities
Drug Discov Today. 2023 Nov 13:103825. doi: 10.1016/j.drudis.2023.103825. Online ahead of print.ABSTRACTWith increasing human life expectancy, the global medical burden of chronic diseases is growing. Hence, chronic diseases are a pressing health concern and will continue to be in decades to come. Chronic diseases often involve multiple malfunctioning organs in the body. An imminent question is how interorgan crosstalk contributes to the etiology of chronic diseases. We conceived the locked-state model (LoSM), which illustrates how interorgan communication can give rise to body-wide memory-like properties that 'lock' healt...
Source: Drug Discovery Today - November 15, 2023 Category: Drugs & Pharmacology Authors: Choong Yong Ung Cristina Correia Hu Li Christopher M Adams Jennifer J Westendorf Shizhen Zhu Source Type: research
