Exploring chemical space for “druglike” small molecules in the age of AI

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: March 17, 2025

The announcement of 2024 Nobel Prize in Chemistry to Alphafold has reiterated the role AI biology and mainly domain "drug discovery". Till few years ago, structure-based drug design (SBDD) been preferred experimental many academic pharmaceutical R D divisions for developing novel therapeutics. However, with advent AI, field especially seen a paradigm shift its R&D across platforms. If design" is game, there are two main players, small molecule target biomolecule, rules governing game based on interactions between these players. In this brief review, we will be discussing our efforts improving state-of-the-art technology respect molecules as well understanding game. review broadly divided into five sections first section introducing challenges faced domain. second section, describe some existing libraries developed labs follow-up more recent knowledge-based resource available public use. four, screening tools laboratories Finally, delves how knowledge utilization design. We provide three case studies from work illustrate work. conclude thoughts future scope

Language: Английский

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Revolutionizing Pharmaceutical Research: Harnessing Machine Learning for a Paradigm Shift in Drug Discovery

International Journal of Multidisciplinary Sciences and Arts, Journal Year: 2023, Volume and Issue: 2(2), P. 149 - 157

Published: Sept. 27, 2023

The fusion of machine learning (ML) and artificial intelligence (AI) is experiencing a dramatic transition in the field pharmaceutical research development. This study examines several effects on different phases medication discovery, development, patient care. capability ML to quickly process huge chemical libraries forecast interactions with target proteins studied, starting compound screening selection. potential for fewer false positives negatives, improved hit prediction accuracy, ensemble technique use are underlined. part that plays enhancing Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) profile then explained. models anticipate actions inside human body by analyzing molecular structures characteristics, improving assessments drug safety efficacy. article goes into further detail about predictive modeling, highlighting how may be used find prospective therapeutic targets confirm their applicability. combination multi-omics data, deep learning, possibility identify similar pathways across diseases highlight game-changing this field. also covers clinical trials, its benefits trial planning, recruitment, real-time monitoring, individualized therapy predictions. By utilizing computational analysis quantum physics, power learning-driven de novo creation examined, revealing develop new candidates. In article, ethical issues surrounding AI-driven discovery discussed, focus necessity transparent data utilization, oversight, responsible consumption. report ends predicting ML's R&D future. Accelerated pipelines, rise customized medicine powered models, optimized change repurposing tactics all envisaged this. emphasizes revolutionary altering development while noting obstacles quality, model interpretability, ethics, interdisciplinary collaboration. It suggested integration AI technologies, cooperation, regulatory modifications essential steps unlock full and, ultimately, provide patients throughout world safer, more efficient, treatments.

Language: Английский

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Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1732 - 1732

Published: Aug. 13, 2023

Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced mortality rate incidence acquired syndrome (AIDS). However, despite remarkable efficacy ART, virologic failure remains a challenge in long-term HIV-infected individuals. Virologic refers to persistent detectable viral load patients receiving indicating an incomplete suppression HIV replication. It can occur due various factors, including poor medication adherence, drug resistance, suboptimal concentrations, interactions, factors such as emergence drug-resistant strains. In recent years, extensive efforts been made understand address order optimize treatment outcomes. Strategies prevent manage include improving adherence through education, counselling, supportive interventions. addition, regular monitoring resistance testing enables early detection facilitates timely adjustments ART regimens. Thus, development novel antiretroviral agents with potency, tolerability, profiles offers new options for experiencing failure. would also face if not managed appropriately. A solution requires comprehensive approach that combines individualized care, robust monitoring, access range drugs.

Language: Английский

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Drug development advances in human genetics‐based targets

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Feb. 1, 2024

Drug development is a long and costly process, with high degree of uncertainty from the identification drug target to its market launch. Targeted drugs supported by human genetic evidence are expected enter phase II/III clinical trials or be approved for marketing more quickly, speeding up process. Currently, data technologies such as genome-wide association studies (GWAS), whole-exome sequencing (WES), whole-genome (WGS) have identified validated many potential molecular targets associated diseases. This review describes structure, biology, genetics-based beneficial loss-of-function (LOF) mutation (target mutations that reduce disease incidence) over past decade. The feasibility eight LOF (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, INHBE) discovery mainly emphasized, their research prospects challenges discussed. In conclusion, we expect this will inspire researchers use genetics genomics support novel therapeutic direction development, which contribute new repurposing.

Language: Английский

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Current applications of intestinal organoids: a review

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 31, 2024

In the past decade, intestinal organoid technology has paved way for reproducing tissue or organ morphogenesis during physiological processes in vitro and studying pathogenesis of various diseases. Intestinal organoids are favored drug screening due to their ability high-throughput cultivation closer resemblance patient genetic characteristics. Furthermore, as disease models, find wide applications diagnostic markers, identifying therapeutic targets, exploring epigenetic mechanisms Additionally, a transplantable cellular system, have played significant role reconstruction damaged epithelium conditions such ulcerative colitis short bowel syndrome, well material exchange metabolic function restoration. The rise interdisciplinary approaches, including organoid-on-chip technology, genome editing techniques, microfluidics, greatly accelerated development organoids. this review, VOSviewer software is used visualize hot co-cited journal keywords trends firstly. Subsequently, we summarized current modeling, screening, regenerative medicine. This will deepen our understanding further explore intestine

Language: Английский

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