Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update

Pharmacological Research, Journal Year: 2019, Volume and Issue: 152, P. 104609 - 104609

Published: Dec. 17, 2019

Language: Английский

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update

Pharmacological Research, Journal Year: 2021, Volume and Issue: 165, P. 105463 - 105463

Published: Jan. 26, 2021

Language: Английский

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Molecular targeted therapy for anticancer treatment

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(10), P. 1670 - 1694

Published: Oct. 12, 2022

Abstract Since the initial clinical approval in late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served a fundamental backbone precision medicine cancer treatment. These approaches are now used clinically first-line various human cancers. Compared to conventional chemotherapy, have efficient with fewer side effects. However, emergence drug resistance is major drawback therapy, several strategies been attempted improve efficacy by overcoming such resistance. Herein, we summarize current knowledge regarding agents, including classification, brief biology target kinases, mechanisms action, examples perspectives future development.

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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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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Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(4), P. 1388 - 1388

Published: Feb. 18, 2020

The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, metastasis formation. Although VEGF-A can activate both VEGFR-1 VEGFR-2 membrane receptors, PlGF VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved physiological pathological the adult required only for angiogenesis. Besides this tumor endothelium, ligand-mediated stimulation of expressed cells may directly induce cell chemotaxis extracellular matrix invasion. Furthermore, activation myeloid progenitors macrophages favors cancer immune escape through release immunosuppressive cytokines. These properties have prompted number preclinical clinical studies analyze involvement metastatic process. aim present review highlight contribution VEGFs/VEGFR-1 signaling progression different types provide overview therapeutic approaches targeting currently under investigation.

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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Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Oct. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Language: Английский

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New developments in the biology of fibroblast growth factors

WIREs Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 14(4)

Published: Feb. 9, 2022

Abstract The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting canonical FGFs and endocrine that activate four receptor tyrosine kinases (FGFRs 1–4) intracellular (intracellular or iFGFs) primarily function to regulate the activity voltage‐gated sodium channels other molecules. FGFs, iFGFs have been reviewed extensively by us others. In this review, we briefly summarize past reviews then focus on new developments in FGF field since our last review 2015. Some highlights 6 years include use optogenetic tools, viral vectors, inducible transgenes experimentally modulate signaling, clinical small molecule FGFR inhibitors, an expanded understanding functions for stem cell pluripotency differentiation, roles tissue homeostasis regeneration, a continuing elaboration mechanisms development, expanding appreciation neuropsychiatric diseases. This article categorized under: Cardiovascular Diseases > Molecular Cellular Physiology Neurological Congenital Stem Cells Development Cancer

Language: Английский

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Deucravacitinib is an allosteric TYK2 protein kinase inhibitor FDA-approved for the treatment of psoriasis

Pharmacological Research, Journal Year: 2023, Volume and Issue: 189, P. 106642 - 106642

Published: Feb. 6, 2023

Psoriasis is a heterogeneous, inflammatory, autoimmune skin disease that affects up to 2% of the world's population. There are many treatment modalities including topical medicines, ultraviolet light therapy, monoclonal antibodies, and several oral medications. Cytokines play central role in pathogenesis this disorder TNF-α, (tumor necrosis factor-α) IL-17A (interleukin-17A), IL-17F, IL-22, IL-23. Cytokine signaling involves transduction mediated by JAK-STAT pathway. four JAKS (JAK1/2/3 TYK2) six STATS (signal transducer activators transcription). Janus kinases contain an inactive JH2 domain aminoterminal active JH1 domain. Under basal conditions, inhibits activity Deucravacitinib orally effective N-trideuteromethyl-pyridazine derivative targets stabilizes TYK2 thereby blocks activity. Seven other JAK inhibitors, which target family domain, prescribed for neoplastic inflammatory diseases. The use deuterium trimethylamide decreases rate demethylation slows production metabolite against variety addition TYK2. A second unique aspect development deucravacitinib targeting pseudokinase rather specific its toxic effects much less than those FDA-approved inhibitors. successful may stimulate additional ligands kinase families as well.

Language: Английский

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