The next-generation Open Targets Platform: reimagined, redesigned, rebuilt

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D1353 - D1359

Published: Nov. 18, 2022

The Open Targets Platform (https://platform.opentargets.org/) is an open source resource to systematically assist drug target identification and prioritisation using publicly available data. Since our last update, we have reimagined, redesigned, rebuilt the in order streamline data integration harmonisation, expand ways which users can explore data, improve user experience. gene-disease causal evidence has been enhanced expanded better capture disease causality across rare, common, somatic diseases. For annotations, incorporated new features that help assess safety tractability, including genetic constraint, PROTACtability assessments, AlphaFold structure predictions. We also introduced machine learning applications for knowledge extraction from published literature, clinical trial information, labels. technologies frameworks since update will ease introduction of creation separate instances adapted requirements. Our Community forum, training materials, outreach programme support a range use cases.

Language: Английский

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Deuterium in drug discovery: progress, opportunities and challenges

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(7), P. 562 - 584

Published: June 5, 2023

Language: Английский

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106552 - 106552

Published: Nov. 17, 2022

Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one most important drug targets 21st century. There are 72 FDA-approved therapeutic agents that target about two dozen different kinases and three these drugs were approved 2022. Of drugs, twelve protein-serine/threonine kinases, four directed against dual specificity (MEK1/2), sixteen block nonreceptor protein-tyrosine 40 receptor kinases. The data indicate 62 prescribed for treatment neoplasms (57 solid tumors breast, lung, colon, ten nonsolid such as leukemia, both tumors: acalabrutinib, ibrutinib, imatinib, midostaurin). Four (abrocitinib, baricitinib, tofacitinib, upadacitinib) used inflammatory (atopic dermatitis, psoriatic arthritis, rheumatoid Crohn disease, ulcerative colitis). eighteen multiple diseases. following received FDA approval 2022 specified diseases: abrocitinib dermatitis), futibatinib (cholangiocarcinomas), pacritinib (myelofibrosis). All orally effective with exception netarsudil, temsirolimus, trilaciclib. This review summarizes physicochemical properties all small molecule inhibitors lipophilic efficiency ligand efficiency.

Language: Английский

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TTD: Therapeutic Target Database describing target druggability information

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D1465 - D1477

Published: Sept. 15, 2023

Target discovery is one of the essential steps in modern drug development, and identification promising targets fundamental for developing first-in-class drug. A variety methods have emerged target assessment based on druggability analysis, which refers to likelihood a being effectively modulated by drug-like agents. In therapeutic database (TTD), nine categories established characteristics were thus collected 426 successful, 1014 clinical trial, 212 preclinical/patented, 1479 literature-reported via systematic review. These characteristic classified into three distinct perspectives: molecular interaction/regulation, human system profile cell-based expression variation. With rapid progression technology concerted effort discovery, TTD other databases highly expected facilitate explorations validation innovative target. now freely accessible at: https://idrblab.org/ttd/.

Language: Английский

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Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 65(2), P. 1047 - 1131

Published: Oct. 8, 2021

The central role of dysregulated kinase activity in the etiology progressive disorders, including cancer, has fostered incremental efforts on drug discovery programs over past 40 years. As a result, inhibitors are today one most important classes drugs. FDA approved 73 small molecule inhibitor drugs until September 2021, and additional were by other regulatory agencies during that time. To complement published literature clinical inhibitors, we have prepared review recaps this large data set into an accessible format for medicinal chemistry community. Along with therapeutic pharmacological properties each across world 2020, provide synthesis routes originally used phase, many which only available patent applications. In last section, also update 2021.

Language: Английский

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update

Pharmacological Research, Journal Year: 2021, Volume and Issue: 175, P. 106037 - 106037

Published: Dec. 15, 2021

Language: Английский

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Deep learning in drug discovery: an integrative review and future challenges

Artificial Intelligence Review, Journal Year: 2022, Volume and Issue: 56(7), P. 5975 - 6037

Published: Nov. 17, 2022

Recently, using artificial intelligence (AI) in drug discovery has received much attention since it significantly shortens the time and cost of developing new drugs. Deep learning (DL)-based approaches are increasingly being used all stages development as DL technology advances, drug-related data grows. Therefore, this paper presents a systematic Literature review (SLR) that integrates recent technologies applications Including, drug-target interactions (DTIs), drug-drug similarity (DDIs), sensitivity responsiveness, drug-side effect predictions. We present more than 300 articles between 2000 2022. The benchmark sets, databases, evaluation measures also presented. In addition, provides an overview how explainable AI (XAI) supports problems. dosing optimization success stories discussed well. Finally, digital twining (DT) open issues suggested future research challenges for Challenges to be addressed, directions identified, extensive bibliography is included.

Language: Английский

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Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 19, 2022

Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies treat have been approved, also discontinued, by United States Food Drug Administration (FDA). To provide an up-to-date account current trends antidiabetic pharmaceuticals, this review offers comprehensive analysis main classes compounds their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type (SGLT2) combinations thereof. The number therapeutic alternatives T2DM now there nearly 60 drugs approved FDA. Beyond 100 additional agents being evaluated in clinical trials. In addition standard treatments therapy metformin, new combinations, e.g., containing SGLT2 dipeptidyl peptidase-4 (DPP4) inhibitors, that gained use during last decade. Furthermore, interesting alternatives, such as lobeglitazone, efpeglenatide tirzepatide, ongoing Modern drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP4 popularity on pharmaceutical market, while less expensive over counter developing economies. large heterogeneity is creating push towards more personalized accessible treatments. We describe trials, which may help achieve near future.

Language: Английский

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update

Pharmacological Research, Journal Year: 2024, Volume and Issue: 200, P. 107059 - 107059

Published: Jan. 11, 2024

Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one most important drug targets 21st century. There are 80 FDA-approved therapeutic agents that target about two dozen different kinases and seven these drugs were approved 2023. Of drugs, thirteen protein-serine/threonine kinases, four directed against dual specificity (MEK1/2), twenty block nonreceptor protein-tyrosine 43 inhibit receptor kinases. The data indicate 69 prescribed for treatment neoplasms. Six (abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, upadacitinib) used inflammatory (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, ulcerative colitis). nearly multiple diseases. following received FDA approval 2023: capivasertib (HER2-positive breast cancer), fruquintinib (metastatic colorectal momelotinib (myelofibrosis), pirtobrutinib (mantle cell lymphoma, chronic lymphocytic leukemia, small lymphoma), quizartinib (Flt3-mutant acute myelogenous leukemia), repotrectinib (ROS1-positive lung ritlecitinib (alopecia areata). All orally effective with exception netarsudil, temsirolimus, trilaciclib. This review summarizes physicochemical properties all molecule inhibitors molecular weight, number hydrogen bond donors/acceptors, polar surface area, potency, solubility, lipophilic efficiency, ligand efficiency.

Language: Английский

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The IUPHAR/BPS Guide to PHARMACOLOGY in 2024

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D1438 - D1449

Published: Oct. 28, 2023

Abstract The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; https://www.guidetopharmacology.org) is an open-access, expert-curated, online database that provides succinct overviews and key references for pharmacological targets their recommended experimental ligands. It includes over 3039 protein 12 163 ligand molecules, including approved drugs, small peptides antibodies. Here, we report recent developments the resource describe expansion in content six releases made during last two years. update section of this paper focuses on areas relating important global health challenges. first, SARS-CoV-2 COVID-19, remains a major concern our efforts expand include new family coronavirus proteins. second area antimicrobial resistance, which have extended coverage antibacterials partnership with AntibioticDB, collaboration has continued through support from GARDP. We discuss other curation also focus external links resources such as PubChem bring synergies resources.

Language: Английский

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