The present state and challenges of active learning in drug discovery
Drug Discov Today. 2024 Apr 18:103985. doi: 10.1016/j.drudis.2024.103985. Online ahead of print.ABSTRACTActive learning (AL) is an iterative feedback process that efficiently identifies valuable data within vast chemical space, even with limited labeled data. This characteristic renders it a valuable approach to tackle the ongoing challenges faced in drug discovery, such as the ever-expanding explore space and the limitations of labeled data. Consequently, AL is increasingly gaining prominence in the field of drug development. In this paper, we comprehensively review the application of AL at all stages of drug discovery, i...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Lei Wang Zhenran Zhou Xixi Yang Shaohua Shi Xiangxiang Zeng Dongsheng Cao Source Type: research
Growing value of data standardization: Allotrope Foundation Connect Workshop Proceedings
Drug Discov Today. 2024 Apr 18:103988. doi: 10.1016/j.drudis.2024.103988. Online ahead of print.ABSTRACTRecent Allotrope Foundation (AF) Connect Workshops (2021-2023) showcased some of the latest advancements in data standardization for analytical data in the pharmaceutical industry. These workshops demonstrated the adaption of two key technologies, the Allotrope Data Format (ADF) and the Allotrope Simple Model (ASM), which streamline instrument data representation and terminology to enhance interoperability across systems. Notably, ASM has facilitated broader adoption of the standard. The increasing significance of data-d...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Henning Kayser Miu-Ling Lau Source Type: research
A new era of antibody discovery: an in-depth review of AI-driven approaches
Drug Discov Today. 2024 Apr 18:103984. doi: 10.1016/j.drudis.2024.103984. Online ahead of print.ABSTRACTGiven their high affinity and specificity for a range of macromolecules, antibodies are widely used in the treatment of autoimmune diseases, cancers, inflammatory diseases, and Alzheimer's disease (AD). Traditional experimental methods are time-consuming, expensive, and labor-intensive. Recent advances in artificial intelligence (AI) technologies provide complementary methods that can reduce the time and costs required for antibody design by minimizing failures and increasing the success rate of experimental tests. In th...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Jin Cheng Tianjian Liang Xiang-Qun Xie Zhiwei Feng Li Meng Source Type: research
Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics
Drug Discov Today. 2024 Apr 18:103986. doi: 10.1016/j.drudis.2024.103986. Online ahead of print.ABSTRACTEED within the PRC2 complex is crucial for chromatin regulation, particularly in tumor development, such that its inhibition is a promising epigenetic therapeutic strategy. Significant advancement in PRC2 inhibitor development has been achieved with an approved EZH2 inhibitor in the market and with others in clinical trials. However, current EZH2 inhibitors are limited to specific blood cancers and encounter therapeutic resistance. EED stabilizes PRC2 and enhances its activity through unique allosteric mechanisms, thereb...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Qichao Bao Anil Kumar Daqing Wu Jia Zhou Source Type: research
The present state and challenges of active learning in drug discovery
Drug Discov Today. 2024 Apr 18:103985. doi: 10.1016/j.drudis.2024.103985. Online ahead of print.ABSTRACTActive learning (AL) is an iterative feedback process that efficiently identifies valuable data within vast chemical space, even with limited labeled data. This characteristic renders it a valuable approach to tackle the ongoing challenges faced in drug discovery, such as the ever-expanding explore space and the limitations of labeled data. Consequently, AL is increasingly gaining prominence in the field of drug development. In this paper, we comprehensively review the application of AL at all stages of drug discovery, i...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Lei Wang Zhenran Zhou Xixi Yang Shaohua Shi Xiangxiang Zeng Dongsheng Cao Source Type: research
Growing value of data standardization: Allotrope Foundation Connect Workshop Proceedings
Drug Discov Today. 2024 Apr 18:103988. doi: 10.1016/j.drudis.2024.103988. Online ahead of print.ABSTRACTRecent Allotrope Foundation (AF) Connect Workshops (2021-2023) showcased some of the latest advancements in data standardization for analytical data in the pharmaceutical industry. These workshops demonstrated the adaption of two key technologies, the Allotrope Data Format (ADF) and the Allotrope Simple Model (ASM), which streamline instrument data representation and terminology to enhance interoperability across systems. Notably, ASM has facilitated broader adoption of the standard. The increasing significance of data-d...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Henning Kayser Miu-Ling Lau Source Type: research
A new era of antibody discovery: an in-depth review of AI-driven approaches
Drug Discov Today. 2024 Apr 18:103984. doi: 10.1016/j.drudis.2024.103984. Online ahead of print.ABSTRACTGiven their high affinity and specificity for a range of macromolecules, antibodies are widely used in the treatment of autoimmune diseases, cancers, inflammatory diseases, and Alzheimer's disease (AD). Traditional experimental methods are time-consuming, expensive, and labor-intensive. Recent advances in artificial intelligence (AI) technologies provide complementary methods that can reduce the time and costs required for antibody design by minimizing failures and increasing the success rate of experimental tests. In th...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Jin Cheng Tianjian Liang Xiang-Qun Xie Zhiwei Feng Li Meng Source Type: research
Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics
Drug Discov Today. 2024 Apr 18:103986. doi: 10.1016/j.drudis.2024.103986. Online ahead of print.ABSTRACTEED within the PRC2 complex is crucial for chromatin regulation, particularly in tumor development, such that its inhibition is a promising epigenetic therapeutic strategy. Significant advancement in PRC2 inhibitor development has been achieved with an approved EZH2 inhibitor in the market and with others in clinical trials. However, current EZH2 inhibitors are limited to specific blood cancers and encounter therapeutic resistance. EED stabilizes PRC2 and enhances its activity through unique allosteric mechanisms, thereb...
Source: Drug Discovery Today - April 20, 2024 Category: Drugs & Pharmacology Authors: Qichao Bao Anil Kumar Daqing Wu Jia Zhou Source Type: research
TPP-based conjugates: potential targeting ligands
Drug Discov Today. 2024 Apr 17:103983. doi: 10.1016/j.drudis.2024.103983. Online ahead of print.ABSTRACTMitochondria are one of the major sources of energy for, as well as regulators of, cancer cell metabolism. Thus, they are potential targets for the effective treatment and management of cancer. Research has explored triphenylphosphonium (TPP) derivatives as potent cancer-targeting ligands because of their lipophilic nature and mitochondrial affinity. In this review, we summarize the utility of TPP-based conjugates targeting mitochondria in different types of cancer and other diseases, such as neurodegenerative and cardio...
Source: Drug Discovery Today - April 19, 2024 Category: Drugs & Pharmacology Authors: Sanya Batheja Shruti Gupta Kiran Kumar Tejavath Umesh Gupta Source Type: research
SETDB1, an H3K9-specific methyltransferase: An attractive epigenetic target to combat cancer
Drug Discov Today. 2024 Apr 16:103982. doi: 10.1016/j.drudis.2024.103982. Online ahead of print.ABSTRACTSET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is an important epigenetic regulator catalyzing histone H3 lysine 9 (H3K9) methylation, specifically di-/tri-methylation. This regulation promotes gene silencing through heterochromatin formation. Aberrant SETDB1 expression, and its oncogenic role is evident in many cancers. Thus, SETDB1 is a valid target with novel therapeutic benefits. In this review, we explore the structural and biochemical features of SETDB1, its regulatory mechanisms, and its role in...
Source: Drug Discovery Today - April 13, 2024 Category: Drugs & Pharmacology Authors: Seema Prashanth Radhika Radha Maniswami Gurukumari Rajajeyabalachandran Sooriya Kumar Jegatheesan Source Type: research
The emerging role of fatty acid binding protein 7 (FABP7) in cancers
Drug Discov Today. 2024 Apr 12;29(5):103980. doi: 10.1016/j.drudis.2024.103980. Online ahead of print.ABSTRACTFatty acid binding protein 7 (FABP7) is an intracellular protein involved in the uptake, transportation, metabolism, and storage of fatty acids (FAs). FABP7 is upregulated up to 20-fold in multiple cancers, usually correlated with poor prognosis. FABP7 silencing or pharmacological inhibition suggest FABP7 promotes cell growth, migration, invasion, colony and spheroid formation/increased size, lipid uptake, and lipid droplet formation. Xenograft studies show that suppression of FABP7 inhibits tumour formation and tu...
Source: Drug Discovery Today - April 13, 2024 Category: Drugs & Pharmacology Authors: William George Warren Myles Osborn Andrew Yates Saoirse E O'Sullivan Source Type: research
Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy
Drug Discov Today. 2024 Apr 16:103981. doi: 10.1016/j.drudis.2024.103981. Online ahead of print.ABSTRACTThe combination of peptides and nanoparticles in cancer therapy has shown synergistic results. Nanoparticle functionalization with peptides can increase their targeting ability towards tumor cells. In some cases, the peptides can develop self-assembled nanoparticles, in combination with drugs, for targeted cancer therapy. The peptides can be loaded into nanoparticles and can be delivered by other drugs for synergistic cancer removal. Multifunctional types of peptide-based nanoparticles, including pH- and redox-sensitive ...
Source: Drug Discovery Today - April 13, 2024 Category: Drugs & Pharmacology Authors: Jingyuan Dai Milad Ashrafizadeh Amir Reza Aref Gautam Sethi Yavuz Nuri Ertas Source Type: research
SETDB1, an H3K9-specific methyltransferase: An attractive epigenetic target to combat cancer
Drug Discov Today. 2024 Apr 11:103982. doi: 10.1016/j.drudis.2024.103982. Online ahead of print.ABSTRACTSET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is an important epigenetic regulator catalyzing histone H3 lysine 9 (H3K9) methylation, specifically di-/tri-methylation. This regulation promotes gene silencing through heterochromatin formation. Aberrant SETDB1 expression, and its oncogenic role is evident in many cancers. Thus, SETDB1 is a valid target with novel therapeutic benefits. In this review, we explore the structural and biochemical features of SETDB1, its regulatory mechanisms, and its role in...
Source: Drug Discovery Today - April 13, 2024 Category: Drugs & Pharmacology Authors: Seema Prashanth Radhika Radha Maniswami Gurukumari Rajajeyabalachandran Sooriya Kumar Jegatheesan Source Type: research
The emerging role of fatty acid binding protein 7 (FABP7) in cancers
Drug Discov Today. 2024 Apr 11:103980. doi: 10.1016/j.drudis.2024.103980. Online ahead of print.ABSTRACTFatty acid binding protein 7 (FABP7) is an intracellular protein involved in the uptake, transportation, metabolism, and storage of fatty acids (FAs). FABP7 is upregulated up to 20-fold in multiple cancers, usually correlated with poor prognosis. FABP7 silencing or pharmacological inhibition suggest FABP7 promotes cell growth, migration, invasion, colony and spheroid formation/increased size, lipid uptake, and lipid droplet formation. Xenograft studies show that suppression of FABP7 inhibits tumour formation and tumour g...
Source: Drug Discovery Today - April 13, 2024 Category: Drugs & Pharmacology Authors: William George Warren Myles Osborn Andy Yates Saoirse E O'Sullivan Source Type: research
Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy
Drug Discov Today. 2024 Apr 11:103981. doi: 10.1016/j.drudis.2024.103981. Online ahead of print.ABSTRACTThe combination of peptides and nanoparticles in cancer therapy has shown synergistic results. Nanoparticle functionalization with peptides can increase their targeting ability towards tumor cells. In some cases, the peptides can develop self-assembled nanoparticles, in combination with drugs, for targeted cancer therapy. The peptides can be loaded into nanoparticles and can be delivered by other drugs for synergistic cancer removal. Multifunctional types of peptide-based nanoparticles, including pH- and redox-sensitive ...
Source: Drug Discovery Today - April 13, 2024 Category: Drugs & Pharmacology Authors: Jingyuan Dai Milad Ashrafizadeh Amir Reza Aref Gautam Sethi Yavuz Nuri Ertas Source Type: research
