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Journal of Enzyme Inhibition and Medicinal Chemistry
Scopus
ISSN 1475-6374 · Taylor & Francis Group · 1.575 artikel di indeks
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Artikel Jurnal
Cynanchum wilfordii modulates inflammatory responses in LPS-stimulated RAW264.7 cells via the NF-κB and MAPK pathways
Cynanchum wilfordii is a widely used herb in Oriental medicine, known for its wide range of therapeutic applications. The present study was conducted with the aim of evaluating the effects of selected compounds isolated from C. wilfordii, including 4-hydroxyacetophenone (CW1)…
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Artikel Jurnal
Identification of a peptide inhibitor disrupting the PCSK9-LDLR interaction via pharmacophore-based virtual screening, molecular dynamics simulations and in vitro/vivo evaluation
The PCSK9-LDLR interaction, driving elevated LDL-C, is a key driver of ASCVD pathogenesis. Identifying peptides disrupting this interaction offers an alternative ASCVD therapy. Herein, via structure-based virtual screening with Pep2-8 as a control, we identified TPP-4, a high-affinity peptide…
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Artikel Jurnal
Synthetic strategies and therapeutic insights into FDA-approved indole-containing drugs
Indole is a privileged heteroaromatic scaffold in medicinal chemistry, characterised by its unique physicochemical properties, hydrogen-bonding potential, and bioisosteric versatility. Over the past decades, numerous indole-containing drugs have been approved by the Food and Drug Administration…
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Artikel Jurnal
Design, synthesis and biological evaluation of donepezil-safinamide hybrids as dual AChE and MAO-B inhibitor for Alzheimer’s disease treatment
Alzheimer’s disease (AD) still lacks therapies that definitively halt its progression. Dual AChE/MAO-B inhibitors offer a promising strategy to address both symptoms and pathology. Here, we designed and synthesised a series of donepezil-safinamide hybrids. The optimised compound 28c was identified…
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Artikel Jurnal
Design, synthesis and biological evaluation of novel KRAS-G12D inhibitors
KRAS-G12D mutations are common drivers of pancreatic and colorectal cancers, yet effective targeted therapies remain limited. This study describes the design, synthesis, and biological evaluation of two novel KRAS-G12D inhibitors, GD-2 and GD-4. Both compounds exhibited strong antiproliferative…
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Thymol carbamates bearing cyclic amines as potent and selective BuChE inhibitors alleviate memory impairments for Alzheimer’s disease therapy
Thymol, an isomer of carvacrol, exhibits anti-Aβ activity. Thymol carbamates were designed, and their inhibition on cholinesterase (ChE) activity was assessed and analysed, among them, TC-4, TC-6, H4 and H5 bearing cyclic amines exhibited nanomolar inhibitory activity with IC50 values of 13, 3.6…
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Artikel Jurnal
Design and optimisation of meta-substituted bis(arylsulfonamido)benzene inhibitors through a molecular hybridisation strategy targeting the Keap1-Nrf2 protein-protein interaction
Nrf2 is recognised as an attractive therapeutic target for oxidative stress-related disorders through its regulation of antioxidant gene transcription. Direct inhibition of Keap1-Nrf2 protein-protein interaction represents a promising strategy to modulate Nrf2 activity. Herein, we report the…
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Artikel Jurnal
Antitumor activity and structure–activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors
Poly(ADP-ribose) polymerase (PARP) inhibitors constitute a significant class of targeted anticancer therapies that leverage the principle of synthetic lethality in tumours deficient in homologous recombination (HR) repair. Although these agents have shown clinical efficacy in treating HR-deficient…
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Artikel Jurnal
Mislocalisation of FLT3-ITD receptor contributes to MV4-11 leukaemia cell resistance to antibody-drug conjugate
FMS-like tyrosine kinase 3 (FLT3/CD135) regulates haematopoiesis and is frequently mutated as FLT3-internal tandem duplication (FLT3-ITD) in acute myeloid leukaemia (AML), associated with poor prognosis. Although FLT3 inhibitors show clinical benefits, resistance remains a challenge. This study…
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Artikel Jurnal
Screening of peptide inhibitors targeting YAP-TEAD4 interaction: affinity evaluation and anti-AML cell activity
Aberrant activation of YAP-TEAD4 drives tumorigenesis, progression, and chemoresistance. Disrupting their interaction serves as an alternative anticancer strategy, with peptides better adapting to the large, flat interaction interface. In this study, the peptides 1–4 were screened from the peptide…
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Artikel Jurnal
Integrating virtual screening and molecular dynamics simulations to identify emodin as a PYCR1 inhibitor modulating docetaxel sensitivity in prostate cancer
Docetaxel (DTX) resistance is the main cause of treatment failure in castration-resistant prostate cancer (CRPC). Pyrroline-5-carboxylic acid reductase 1 (PYCR1) is an enzyme involved in proline metabolism. It is highly expressed in various cancers and promotes malignant progression, yet its role…
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Artikel Jurnal
Design, synthesis and antiproliferative activity of oxadiazole derivatives as potent glycogen synthase kinase-3/histone deacetylase 6 dual inhibitors
A series of oxadiazole-based dual inhibitors targeting GSK3 and HDAC6 were rationally designed by integrating key pharmacophores into a single molecule. Among these derivatives, 4-(((5-(benzo[d][1, 3]dioxol-5-yl)-1,3,4-oxadiazol-2-yl)thio)methyl)-N-hydroxybenzamide (15i) was identified as the most…
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Artikel Jurnal
Porcine serum maltase-glucoamylase: structure, kinetics, and inhibition
Maltase-glucoamylase (MGAM) is a small-intestinal enzyme comprising two tandem α-glucosidase units, NtMGAM and CtMGAM, each capable of hydrolysing maltodextrins into glucose. MGAM serves as a therapeutic target for managing postprandial hyperglycaemia; comprehensive insights into its full-length…
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Artikel Jurnal
Design, synthesis and anti-breast cancer activity evaluation of 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine-based PARP1/ATR dual inhibitors
PARP1 inhibitors are FDA-approved for BRCA1/2-mutated breast cancer but show limited efficacy in wild-type cancers and face resistance issues. To overcome these, we designed novel 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine-based compounds integrating PARP1 inhibitor pharmacophores with the ATR…
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Artikel Jurnal
Palladium-catalysed synthesis of small-molecule epigenetic inhibitors as anticancer therapeutics
Palladium-catalysed reactions have emerged as indispensable tools in medicinal chemistry, enabling the precise construction of C-C and C-N bonds across a wide spectrum of drug-like molecular frameworks. This manuscript comprehensively examines advances reported over the past five years in…
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Artikel Jurnal
Diethyl Phthalate (DEP) as a potential osteosarcoma risk factor: a multi-omics study integrating network Toxicology, single-cell RNA sequencing, and molecular docking
Diethyl phthalate (DEP), a common plasticiser and endocrine disruptor, has been linked to cancer, but its role in osteosarcoma (OS) remains unclear. This study integrated network toxicology, transcriptomics, protein-protein interaction (PPI) analysis, machine learning, molecular docking, molecular…
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Artikel Jurnal
Application of 18β-glycyrrhetinic acid Fluorescent probes in cell imaging
Fluorescently labelled small molecule probes (fluorescent probes) play an important role in cell imaging and are often used in combination with light-affinity probes to determine the subcellular localisation of target proteins. To investigate the target proteins of 18β-glycyrrhetinic acid (18β-GA)…
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Artikel Jurnal
Pesticidal evaluation of novel dual-chiral N-cyano sulfiliminyl anthranilic diamides derivatives
To develop eco-friendly pesticides with novel modes of action for insect management, a series of dual-chiral N-cyano sulfilimine-substituted anthranilic diamides were designed and synthesised de novo, and their insecticidal activities were evaluated against Mythimna separata (M. separata) and…
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Artikel Jurnal
Discovery of novel coumarin-containing triazolo[1,5-a]pyrimidine derivatives as potent ABCB1 inhibitor for modulation of multidrug resistance
ABCB1-mediated drug efflux is a key determinant of multidrug resistance (MDR) in cancer. To overcome this mechanism, a series of thiol-substituted aminocoumarin-derived, coumarin-containing triazolo[1,5-a]pyrimidine derivatives (5a-5s) was synthesised, and compound 5r (NYH-707) was identified as…
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Artikel Jurnal
Reactive oxygen species (ROS) research in drug discovery and drug delivery: Can the medium Be a Trojan Horse disguised as something benign?
In studying the roles of reactive oxygen species (ROS) in various biological processes, the availability of appropriate cell culture models is critical. Addition of H2O2 to cells is commonly used to simulate oxidative stress. In doing so, generation of highly reactive oxygen species (hROS) in cell…
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