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Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors
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Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 26678

Special Issue Editors

Prof. Dr. Fen Er Chen

E-Mail Website
Guest Editor
Department of Chemistry, Fudan University, Shanghai, China
Interests: drug design; anti-HIV; NNRTI; continuous flow chemistry; green synthesis and catalysis
Dr. Shuai Wang

E-Mail Website
Guest Editor Assistant
Department of Chemistry, Fudan University, Shanghai, China
Interests: drug design; anticancer; anti-HIV; NNRTI; combinatorial chemistry strategies

Special Issue Information

Dear Colleagues,

Enzyme inhibitors have been widely studied in the field of drug discovery and development due to their potential therapeutic applications. Inhibiting enzymes that are involved in disease pathways can lead to the development of new drugs for the treatment of various diseases. The synthesis and evaluation of bioactivity of enzyme inhibitors is an important area of research that involves the design, synthesis, and testing of compounds that can selectively inhibit specific enzymes. This Special Issue aims to highlight recent advances in the synthesis and evaluation of bioactivity of enzyme inhibitors. As the guest editor, I am excited to present a collection of articles that cover a range of topics related to enzyme inhibitors, including the design and synthesis of novel inhibitors, the evaluation of their bioactivity, and their potential therapeutic applications. Overall, this Special Issue provides a comprehensive overview of the current state of research in the field of enzyme inhibitors, which will be of interest to researchers in medicinal chemistry, biochemistry, and agriculture, as well as to anyone interested in the development of new drugs and crop protection agents. We welcome high-quality reviews or research articles for this Special Issue. The topics of this Special Issue include, but are not limited to, the following:

  • Drug repositioning;
  • Application of privileged structures in drug design;
  • New methods and new strategies to quickly discover drug candidates;
  • Proteolysis targeting chimeras (PROTACs);
  • Identification of inhibitors of new enzyme targets;
  • Recent advance in medicinal chemistry.

Prof. Dr. Fen Er Chen
Guest Editor

Dr. Shuai Wang
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • new targets
  • new mechanisms
  • new strategies
  • drug design
  • PROTACs

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Published Papers (11 papers)

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Research

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19 pages, 2984 KiB  
Article
Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors
by Yiying Zhang, Rao Wang, Yueyue Bu, Angela Corona, Laura Dettori, Enzo Tramontano, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Ge Meng and Fen-Er Chen
Molecules 2025, 30(9), 1868; https://doi.org/10.3390/molecules30091868 - 22 Apr 2025
Viewed by 233
Abstract
Targeting ribonuclease H (RNase H) has emerged as a highly promising strategy for treating HIV-1. In this study, a series of novel 3-hydrazonoindolin-2-one derivatives were designed and synthesized as potential inhibitors of HIV-1 RNase H. Notably, several of these derivatives displayed micromolar inhibitory [...] Read more.
Targeting ribonuclease H (RNase H) has emerged as a highly promising strategy for treating HIV-1. In this study, a series of novel 3-hydrazonoindolin-2-one derivatives were designed and synthesized as potential inhibitors of HIV-1 RNase H. Notably, several of these derivatives displayed micromolar inhibitory activity. Among the compounds examined, the hit compound demonstrated potent inhibition of HIV-1 RNase H, boasting a Ki value of 2.31 μM. Additionally, the most potent compound of this general structure exhibited remarkable inhibitory activity, with Ki values of 0.55 μM. Through docking studies, the key interactions of this ligand within the active site of RNase H were uncovered. This novel chemical structure can be regarded as a prospective scaffold for the future development of RNase H inhibitors. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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23 pages, 4780 KiB  
Article
Triazole-Estradiol Analogs Induce Apoptosis and Inhibit EGFR and Its Downstream Pathways in Triple Negative Breast Cancer
by Felix Acheampong, Trevor Ostlund, Emily Hedge, Jacqueline Laddusaw, Faez Alotaibi, Yaseen A. M. M. Elshaier and Fathi Halaweish
Molecules 2025, 30(3), 605; https://doi.org/10.3390/molecules30030605 - 30 Jan 2025
Viewed by 963
Abstract
Triple negative breast cancer, TNBC, is a difficult disease to treat due to relapse and resistance to known therapies. Epidermal growth factor receptor (EGFR), a tyrosine kinase responsible for downstream signaling leading to cell growth and survival, is typically overexpressed in TNBC. Our [...] Read more.
Triple negative breast cancer, TNBC, is a difficult disease to treat due to relapse and resistance to known therapies. Epidermal growth factor receptor (EGFR), a tyrosine kinase responsible for downstream signaling leading to cell growth and survival, is typically overexpressed in TNBC. Our previous work has detailed the synthesis of triazole-estradiol derivatives as inhibitors of EGFR and downstream receptors, and this work continues that discussion by evaluating them in EGFR-dependent TNBC cell models MDA-MB-231 and MDA-MB-468. Compound Fz25 was cytotoxic against both MDA-MB-231 and MDA-MB-468 cell lines, yielding IC50 values of 8.12 ± 0.85 and 25.43 ± 3.68 µM, respectively. However, compounds Fz57 and Fz200 were potent against only MDA-MB-231 cells, generating IC50 values of 21.18 ± 0.23 and 10.86 ± 0.69 µM, respectively. Pathway analyses revealed that Fz25, Fz57 and Fz200 arrested the G0/G1 phase of the cell cycle and concomitantly suppressed cell cycle regulators, cyclin D1, cyclin E and Dyrk1B in MDA-MB-231 cells. Additionally, all compounds inhibited EGFR and its downstream signaling pathways—extracellular receptor kinase (ERK) and the mammalian target of rapamycin (mTOR)—in a dose-dependent manner. Furthermore, Fz25, Fz57 and Fz200 induced apoptosis in MDA-MB-231 cells by modulating morphological changes, including chromatin condensation, and attenuating the levels of cytochrome c, APAF1, caspases-3 and -9 as well as cleaved PARP. Of these compounds, only Fz25 showed overall satisfactory ADMET properties in silico. Similarly, Fz25 showed suitable binding parameters explored using molecular dynamic simulations in silico. These findings suggest that Fz25 warrants further preclinical and clinical investigations as a new generation of triazole congeners with significant potency in EFGR-dependent TNBC. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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17 pages, 1816 KiB  
Article
The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Plasmodium falciparum Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying N-Substituents
by Sana Takada, Mona A. Abdullaziz, Stefan Höfmann, Talea Knak, Shin-ichiro Ozawa, Yasumitsu Sakamoto, Thomas Kurz and Nobutada Tanaka
Molecules 2025, 30(1), 72; https://doi.org/10.3390/molecules30010072 - 28 Dec 2024
Viewed by 820
Abstract
It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of Plasmodium falciparum by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse [...] Read more.
It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of Plasmodium falciparum by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against PfDXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the N-phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of PfDXR. In this study, the crystal structures of PfDXR in complex with a series of reverse N-phenylalkyl derivatives of fosmidomycin were determined to ascertain whether the high inhibitory activities of the derivatives are consistently attributable to the utilization of the subpocket of PfDXR. While all reverse fosmidomycin derivatives with an N-substituted phenylalkyl group exhibit potent inhibitory activity against PfDXR, the present crystal structure analyses revealed that their binding modes to the PfDXR are not uniform. In these compounds, the nanomolar inhibitory activities appear to be driven by binding modes distinct from that observed for the inhibitor containing the N-phenylpropyl group. The structural information obtained in this study will provide a basis for further design of fosmidomycin derivatives. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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17 pages, 3790 KiB  
Article
Structure-Based Design of Novel Thiazolone[3,2-a]pyrimidine Derivatives as Potent RNase H Inhibitors for HIV Therapy
by Xuan-De Zhu, Angela Corona, Stefania Maloccu, Enzo Tramontano, Shuai Wang, Christophe Pannecouque, Erik De Clercq, Ge Meng and Fen-Er Chen
Molecules 2024, 29(9), 2120; https://doi.org/10.3390/molecules29092120 - 3 May 2024
Cited by 4 | Viewed by 1578
Abstract
Ribonuclease H (RNase H) was identified as an important target for HIV therapy. Currently, no RNase H inhibitors have reached clinical status. Herein, a series of novel thiazolone[3,2-a]pyrimidine-containing RNase H inhibitors were developed, based on the hit compound 10i, identified [...] Read more.
Ribonuclease H (RNase H) was identified as an important target for HIV therapy. Currently, no RNase H inhibitors have reached clinical status. Herein, a series of novel thiazolone[3,2-a]pyrimidine-containing RNase H inhibitors were developed, based on the hit compound 10i, identified from screening our in-house compound library. Some of these derivatives exhibited low micromolar inhibitory activity. Among them, compound 12b was identified as the most potent inhibitor of RNase H (IC50 = 2.98 μM). The experiment of magnesium ion coordination was performed to verify that this ligand could coordinate with magnesium ions, indicating its binding ability to the catalytic site of RNase H. Docking studies revealed the main interactions of this ligand with RNase H. A quantitative structure activity relationship (QSAR) was also conducted to disclose several predictive mathematic models. A molecular dynamics simulation was also conducted to determine the stability of the complex. Taken together, thiazolone[3,2-a]pyrimidine can be regarded as a potential scaffold for the further development of RNase H inhibitors. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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14 pages, 3333 KiB  
Article
Rivastigmine–Bambuterol Hybrids as Selective Butyrylcholinesterase Inhibitors
by Jie Wu, Zekai Tan, Marco Pistolozzi and Wen Tan
Molecules 2024, 29(1), 72; https://doi.org/10.3390/molecules29010072 - 22 Dec 2023
Cited by 2 | Viewed by 1914
Abstract
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer’s disease. In this work, one rivastigmine–bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent [...] Read more.
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer’s disease. In this work, one rivastigmine–bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC50(AChE) > 100,000 nM, IC50(BChE) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood–brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer’s disease. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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13 pages, 3072 KiB  
Article
Design, Synthesis, and Antiproliferative Activity of Selective Histone Deacetylases 6 Inhibitors Containing a Tetrahydropyridopyrimidine Scaffold
by Bin Wang, Youcai Liu, Lejing Zhang, Yajuan Wang, Zhaoxi Li and Xin Chen
Molecules 2023, 28(21), 7323; https://doi.org/10.3390/molecules28217323 - 29 Oct 2023
Cited by 2 | Viewed by 1267
Abstract
The development of selective histone deacetylase 6 inhibitors (sHDAC6is) is being recognized as a therapeutic approach for cancers. In this paper, we designed a series of novel tetrahydropyridopyrimidine derivatives as sHDAC6 inhibitors. The most potent compound, 8-(2, 4-bis(3-methoxyphenyl)-5, 8-dihydropyrido [3, 4-d]pyrimidin-7(6 [...] Read more.
The development of selective histone deacetylase 6 inhibitors (sHDAC6is) is being recognized as a therapeutic approach for cancers. In this paper, we designed a series of novel tetrahydropyridopyrimidine derivatives as sHDAC6 inhibitors. The most potent compound, 8-(2, 4-bis(3-methoxyphenyl)-5, 8-dihydropyrido [3, 4-d]pyrimidin-7(6H)-yl)-N-hydroxy-8-oxooctanamide (8f), inhibited HDAC6 with IC50 of 6.4 nM, and showed > 48-fold selectivity over other subtypes. In Western blot assay, 8f elevated the levels of acetylated α-tubulin in a dose-dependent manner. In vitro, 8f inhibited RPMI-8226, HL60, and HCT116 tumor cells with IC50 of 2.8, 3.20, and 3.25 μM, respectively. Moreover, 8f showed good antiproliferative activity against a panel of tumor cells. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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Review

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16 pages, 1665 KiB  
Review
Enzyme Inhibitors as Multifaceted Tools in Medicine and Agriculture
by Sonia Del Prete and Mario Pagano
Molecules 2024, 29(18), 4314; https://doi.org/10.3390/molecules29184314 - 11 Sep 2024
Viewed by 3747
Abstract
Enzymes are molecules that play a crucial role in maintaining homeostasis and balance in all living organisms by catalyzing metabolic and cellular processes. If an enzyme’s mechanism of action is inhibited, the progression of certain diseases can be slowed or halted, making enzymes [...] Read more.
Enzymes are molecules that play a crucial role in maintaining homeostasis and balance in all living organisms by catalyzing metabolic and cellular processes. If an enzyme’s mechanism of action is inhibited, the progression of certain diseases can be slowed or halted, making enzymes a key therapeutic target. Therefore, identifying or developing enzyme inhibitors is essential for treating significant diseases and ensuring plant defense against pathogens. This review aims to compile information on various types of enzyme inhibitors, particularly those that are well studied and beneficial in both human and plant contexts, by analyzing their mechanisms of action and the resulting benefits. Specifically, this review focuses on three different types of enzyme inhibitors that are most studied, recognized, and cited, each with distinct areas of action and potential benefits. For instance, serine enzyme inhibitors in plants help defend against pathogens, while the other two classes—alpha-glucosidase inhibitors and carbonic anhydrase inhibitors—have significant effects on human health. Furthermore, this review is also intended to assist other researchers by providing valuable insights into the biological effects of specific natural or synthetic inhibitors. Based on the current understanding of these enzyme inhibitors, which are among the most extensively studied in the scientific community, future research could explore their use in additional applications or the development of synthetic inhibitors derived from natural ones. Such inhibitors could aid in defending against pathogenic organisms, preventing the onset of diseases in humans, or even slowing the growth of certain pathogenic microorganisms. Notably, carbonic anhydrase inhibitors have shown promising results in potentially replacing antibiotics, thereby addressing the growing issue of antibiotic resistance. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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23 pages, 3494 KiB  
Review
Synthetic Approaches and Clinical Application of Representative Small-Molecule Inhibitors of Cyclin-Dependent Kinase for Cancer Therapy
by Ya-Tao Wang, Shi-Qi Jiang and Shao-Lin Zhang
Molecules 2024, 29(13), 3029; https://doi.org/10.3390/molecules29133029 - 26 Jun 2024
Viewed by 2604
Abstract
The regulation of the cancer cell cycle heavily relies on cyclin-dependent kinases (CDKs). Targeting CDKs has been identified as a promising approach for effective cancer therapy. In recent years, there has been significant attention paid towards developing small-molecule CDK inhibitors in the field [...] Read more.
The regulation of the cancer cell cycle heavily relies on cyclin-dependent kinases (CDKs). Targeting CDKs has been identified as a promising approach for effective cancer therapy. In recent years, there has been significant attention paid towards developing small-molecule CDK inhibitors in the field of drug discovery. Notably, five such inhibitors have already received regulatory approval for the treatment of different cancers, including breast tumors, lung malignancies, and hematological malignancies. This review provides an overview of the synthetic routes used to produce 17 representative small-molecule CDK inhibitors that have obtained regulatory approval or are currently being evaluated through clinical trials. It also discusses their clinical applications for treating CDK-related diseases and explores the challenges and limitations associated with their use in a clinical setting, which will stimulate the further development of novel CDK inhibitors. By integrating therapeutic applications, synthetic methodologies, and mechanisms of action observed in various clinical trials involving these CDK inhibitors, this review facilitates a comprehensive understanding of the versatile roles and therapeutic potential offered by interventions targeting CDKs. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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30 pages, 4067 KiB  
Review
Synthetic Routes and Clinical Application of Representative Small-Molecule EGFR Inhibitors for Cancer Therapy
by Ya-Tao Wang, Peng-Cheng Yang, Jing-Yi Zhang and Jin-Feng Sun
Molecules 2024, 29(7), 1448; https://doi.org/10.3390/molecules29071448 - 23 Mar 2024
Cited by 4 | Viewed by 4137
Abstract
The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR [...] Read more.
The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic. The synthetic methods and associated challenges pertaining to these compounds are thoroughly examined, along with innovative strategies to overcome these obstacles. Furthermore, the review discusses the clinical applications of FDA-approved EGFR inhibitors such as erlotinib, gefitinib, afatinib, and osimertinib across various cancer types and their corresponding clinical outcomes. Additionally, it addresses the emergence of resistance mechanisms and potential counterstrategies. Taken together, this review aims to provide valuable insights for researchers, clinicians, and pharmaceutical scientists interested in comprehending the current landscape of small-molecule EGFR inhibitors. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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45 pages, 6382 KiB  
Review
Catalysts of Healing: A Symphony of Synthesis and Clinical Artistry in Small-Molecule Agents for Breast Cancer Alleviation
by Jing Hu, Bi-Yue Zhu and Zhen-Xi Niu
Molecules 2024, 29(5), 1166; https://doi.org/10.3390/molecules29051166 - 5 Mar 2024
Viewed by 3302
Abstract
Breast cancer, characterized by its molecular intricacy, has witnessed a surge in targeted therapeutics owing to the rise of small-molecule drugs. These entities, derived from cutting-edge synthetic routes, often encompassing multistage reactions and chiral synthesis, target a spectrum of oncogenic pathways. Their mechanisms [...] Read more.
Breast cancer, characterized by its molecular intricacy, has witnessed a surge in targeted therapeutics owing to the rise of small-molecule drugs. These entities, derived from cutting-edge synthetic routes, often encompassing multistage reactions and chiral synthesis, target a spectrum of oncogenic pathways. Their mechanisms of action range from modulating hormone receptor signaling and inhibiting kinase activity, to impeding DNA damage repair mechanisms. Clinical applications of these drugs have resulted in enhanced patient survival rates, reduction in disease recurrence, and improved overall therapeutic indices. Notably, certain molecules have showcased efficacy in drug-resistant breast cancer phenotypes, highlighting their potential in addressing treatment challenges. The evolution and approval of small-molecule drugs have ushered in a new era for breast cancer therapeutics. Their tailored synthetic pathways and defined mechanisms of action have augmented the precision and efficacy of treatment regimens, paving the way for improved patient outcomes in the face of this pervasive malignancy. The present review embarks on a detailed exploration of small-molecule drugs that have secured regulatory approval for breast cancer treatment, emphasizing their clinical applications, synthetic pathways, and distinct mechanisms of action. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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21 pages, 6396 KiB  
Review
A Comprehensive Review of Small-Molecule Inhibitors Targeting Bruton Tyrosine Kinase: Synthetic Approaches and Clinical Applications
by Qi Zhang, Changming Wen, Lijie Zhao and Yatao Wang
Molecules 2023, 28(24), 8037; https://doi.org/10.3390/molecules28248037 - 11 Dec 2023
Cited by 3 | Viewed by 5039
Abstract
Bruton tyrosine kinase (BTK) is an essential enzyme in the signaling pathway of the B-cell receptor (BCR) and is vital for the growth and activation of B-cells. Dysfunction of BTK has been linked to different types of B-cell cancers, autoimmune conditions, and inflammatory [...] Read more.
Bruton tyrosine kinase (BTK) is an essential enzyme in the signaling pathway of the B-cell receptor (BCR) and is vital for the growth and activation of B-cells. Dysfunction of BTK has been linked to different types of B-cell cancers, autoimmune conditions, and inflammatory ailments. Therefore, focusing on BTK has become a hopeful approach in the field of therapeutics. Small-molecule inhibitors of BTK have been developed to selectively inhibit its activity and disrupt B-cell signaling pathways. These inhibitors bind to the active site of BTK and prevent its phosphorylation, leading to the inhibition of downstream signaling cascades. Regulatory authorities have granted approval to treat B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with multiple small-molecule BTK inhibitors. This review offers a comprehensive analysis of the synthesis and clinical application of conventional small-molecule BTK inhibitors at various clinical stages, as well as presents promising prospects for the advancement of new small-molecule BTK inhibitors. Full article
(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)
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