Formulation strategies for the development of high drug-loaded amorphous solid dispersions
Drug Discov Today. 2023 Oct 25:103806. doi: 10.1016/j.drudis.2023.103806. Online ahead of print.ABSTRACTAmorphous solid dispersions (ASD) have gained tremendous attention over the past two decades as one of the most promising techniques for enhancing the solubility of poorly water-soluble drugs. However, low drug loading is one of the major challenges of ASD technology that limits its commercialization to only a few drug candidates. Increasing the drug loading increases the risk of recrystallization during storage (solid state) and/or during dissolution (solution state). Various formulation and process-related strategies h...
Source: Drug Discovery Today - October 27, 2023 Category: Drugs & Pharmacology Authors: Hemanth Mamidi Siddhant Palekar Henis Patel Pavan Kumar Nukala Ketan Patel Source Type: research
Illuminating the druggable genome: Pathways to progress
Drug Discov Today. 2023 Oct 25:103805. doi: 10.1016/j.drudis.2023.103805. Online ahead of print.ABSTRACTThere are ∼4500 genes within the 'druggable genome', the subset of the human genome that expresses proteins able to bind drug-like molecules, yet existing drugs only target a few hundred. A substantial subset of druggable proteins are largely uncharacterized or understudied, with many falling within G protein-coupled receptor (GPCR), ion channel, and kinase protein families. To improve scientific understanding of these three understudied protein families, the US National Institutes of Health launched the Illuminating t...
Source: Drug Discovery Today - October 27, 2023 Category: Drugs & Pharmacology Authors: Karlie R Sharma Christine M Colvis Griffin P Rodgers Douglas M Sheeley Source Type: research
Promising new pharmacological targets for depression: the search for efficacy
Drug Discov Today. 2023 Oct 19:103804. doi: 10.1016/j.drudis.2023.103804. Online ahead of print.ABSTRACTPharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD and their problems,...
Source: Drug Discovery Today - October 21, 2023 Category: Drugs & Pharmacology Authors: Lucila Emiko Tsugiyama Ruan Carlos Macedo Moraes Yaslle Andrade Cavalcante Moraes Jose Francis-Oliveira Source Type: research
Promising new pharmacological targets for depression: the search for efficacy
Drug Discov Today. 2023 Oct 19:103804. doi: 10.1016/j.drudis.2023.103804. Online ahead of print.ABSTRACTPharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD and their problems,...
Source: Drug Discovery Today - October 21, 2023 Category: Drugs & Pharmacology Authors: Lucila Emiko Tsugiyama Ruan Carlos Macedo Moraes Yaslle Andrade Cavalcante Moraes Jose Francis-Oliveira Source Type: research
Promising new pharmacological targets for depression: the search for efficacy
Drug Discov Today. 2023 Oct 19:103804. doi: 10.1016/j.drudis.2023.103804. Online ahead of print.ABSTRACTPharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD and their problems,...
Source: Drug Discovery Today - October 21, 2023 Category: Drugs & Pharmacology Authors: Lucila Emiko Tsugiyama Ruan Carlos Macedo Moraes Yaslle Andrade Cavalcante Moraes Jose Francis-Oliveira Source Type: research
Promising new pharmacological targets for depression: the search for efficacy
Drug Discov Today. 2023 Oct 19:103804. doi: 10.1016/j.drudis.2023.103804. Online ahead of print.ABSTRACTPharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD and their problems,...
Source: Drug Discovery Today - October 21, 2023 Category: Drugs & Pharmacology Authors: Lucila Emiko Tsugiyama Ruan Carlos Macedo Moraes Yaslle Andrade Cavalcante Moraes Jose Francis-Oliveira Source Type: research
Promising new pharmacological targets for depression: the search for efficacy
Drug Discov Today. 2023 Oct 19:103804. doi: 10.1016/j.drudis.2023.103804. Online ahead of print.ABSTRACTPharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD and their problems,...
Source: Drug Discovery Today - October 21, 2023 Category: Drugs & Pharmacology Authors: Lucila Emiko Tsugiyama Ruan Carlos Macedo Moraes Yaslle Andrade Cavalcante Moraes Jose Francis-Oliveira Source Type: research
Anti-amyloid potential of some phytochemicals against A β-peptide and α-synuclein, tau, prion, and Huntington proteins
Drug Discov Today. 2023 Oct 17:103802. doi: 10.1016/j.drudis.2023.103802. Online ahead of print.ABSTRACTSome molecules self-assemble to create complex structures through molecular self-assembly. Hydrogel preparation, tissue repair, and therapeutic drug delivery are a few applications of molecular self-assembly. However, the self-assembly of amino acids, peptides, and proteins forms amyloid fibrils, resulting in various disorders, most notably neurodegenerative ailments. Examples include the self-assembly of phenylalanine, which causes phenylketonuria; Aβ, which causes Alzheimer's disease; the tau protein, which causes bot...
Source: Drug Discovery Today - October 20, 2023 Category: Drugs & Pharmacology Authors: Jenat Pazheparambil Jerom Soorylekshmi Madhukumar Raveendran Harikumaran Nair Sunilkumar Puthenpurackal Narayanan Source Type: research
Microneedle-mediated drug delivery for scar prevention and treatment
Drug Discov Today. 2023 Oct 17:103801. doi: 10.1016/j.drudis.2023.103801. Online ahead of print.ABSTRACTScars are an inevitable natural outcome of most wound healing processes and affect skin functions, leading to cosmetic, psychological and social problems. Several strategies, including surgery, radiation, cryotherapy, laser therapy, pressure therapy and corticosteroids, can be used to either prevent or treat scars. However, these strategies are ineffective, have side effects and are typically expensive. Microneedle (MN) technology is a powerful, minimally invasive platform for transdermal drug delivery. This review discu...
Source: Drug Discovery Today - October 20, 2023 Category: Drugs & Pharmacology Authors: Bricard Mbituyimana Clemence Futila Bukatuka Fuyu Qi Guangrui Ma Zhijun Shi Guang Yang Source Type: research
Anti-amyloid potential of some phytochemicals against A β-peptide and α-synuclein, tau, prion, and Huntington proteins
Drug Discov Today. 2023 Oct 17:103802. doi: 10.1016/j.drudis.2023.103802. Online ahead of print.ABSTRACTSome molecules self-assemble to create complex structures through molecular self-assembly. Hydrogel preparation, tissue repair, and therapeutic drug delivery are a few applications of molecular self-assembly. However, the self-assembly of amino acids, peptides, and proteins forms amyloid fibrils, resulting in various disorders, most notably neurodegenerative ailments. Examples include the self-assembly of phenylalanine, which causes phenylketonuria; Aβ, which causes Alzheimer's disease; the tau protein, which causes bot...
Source: Drug Discovery Today - October 20, 2023 Category: Drugs & Pharmacology Authors: Jenat Pazheparambil Jerom Soorylekshmi Madhukumar Raveendran Harikumaran Nair Sunilkumar Puthenpurackal Narayanan Source Type: research
Microneedle-mediated drug delivery for scar prevention and treatment
Drug Discov Today. 2023 Oct 17:103801. doi: 10.1016/j.drudis.2023.103801. Online ahead of print.ABSTRACTScars are an inevitable natural outcome of most wound healing processes and affect skin functions, leading to cosmetic, psychological and social problems. Several strategies, including surgery, radiation, cryotherapy, laser therapy, pressure therapy and corticosteroids, can be used to either prevent or treat scars. However, these strategies are ineffective, have side effects and are typically expensive. Microneedle (MN) technology is a powerful, minimally invasive platform for transdermal drug delivery. This review discu...
Source: Drug Discovery Today - October 20, 2023 Category: Drugs & Pharmacology Authors: Bricard Mbituyimana Clemence Futila Bukatuka Fuyu Qi Guangrui Ma Zhijun Shi Guang Yang Source Type: research
Advances in developing noncovalent small molecules targeting Keap1
Drug Discov Today. 2023 Oct 16:103800. doi: 10.1016/j.drudis.2023.103800. Online ahead of print.ABSTRACTKelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharm...
Source: Drug Discovery Today - October 18, 2023 Category: Drugs & Pharmacology Authors: Marilia Barreca Yuting Qin Marie Elodie H élène Cadot Paola Barraja Anders Bach Source Type: research
Pharmacologically targeting intracellular allosteric sites of GPCRs for drug discovery
Drug Discov Today. 2023 Oct 16:103803. doi: 10.1016/j.drudis.2023.103803. Online ahead of print.ABSTRACTG-protein-coupled receptors (GPCRs) are a family of cell surface proteins that can sense a variety of extracellular stimuli and mediate multiple signaling transduction pathways involved in human physiology. Recent advances in GPCR structural biology have revealed a relatively conserved intracellular allosteric site in multiple GPCRs, which can be utilized to modulate receptors from the inside. This novel intracellular site partially overlaps with the G-protein and β-arrestin coupling sites, providing a novel avenue for ...
Source: Drug Discovery Today - October 18, 2023 Category: Drugs & Pharmacology Authors: Mingyang Zhang Xiaobing Lan Xiaolong Li Shaoyong Lu Source Type: research
Advances in developing noncovalent small molecules targeting Keap1
Drug Discov Today. 2023 Oct 16:103800. doi: 10.1016/j.drudis.2023.103800. Online ahead of print.ABSTRACTKelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharm...
Source: Drug Discovery Today - October 18, 2023 Category: Drugs & Pharmacology Authors: Marilia Barreca Yuting Qin Marie Elodie H élène Cadot Paola Barraja Anders Bach Source Type: research
Pharmacologically targeting intracellular allosteric sites of GPCRs for drug discovery
Drug Discov Today. 2023 Oct 16:103803. doi: 10.1016/j.drudis.2023.103803. Online ahead of print.ABSTRACTG-protein-coupled receptors (GPCRs) are a family of cell surface proteins that can sense a variety of extracellular stimuli and mediate multiple signaling transduction pathways involved in human physiology. Recent advances in GPCR structural biology have revealed a relatively conserved intracellular allosteric site in multiple GPCRs, which can be utilized to modulate receptors from the inside. This novel intracellular site partially overlaps with the G-protein and β-arrestin coupling sites, providing a novel avenue for ...
Source: Drug Discovery Today - October 18, 2023 Category: Drugs & Pharmacology Authors: Mingyang Zhang Xiaobing Lan Xiaolong Li Shaoyong Lu Source Type: research
