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Article
Open AccessA novel HSP90 inhibitor SL-145 suppresses metastatic triple-negative breast cancer without triggering the heat shock response
Despite recent advances, there remains a significant unmet need for the development of new targeted therapies for triple-negative breast cancer (TNBC). Although the heat shock protein HSP90 is a promising targ...
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Article
Open AccessStructural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists
Diacylglycerol (DAG) is a versatile lipid whose 1,2-sn-stereoisomer serves both as second messenger in signal transduction pathways that control vital cellular processes, and as metabolic precursor for downstream...
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Article
Open AccessThe C-terminal HSP90 inhibitor NCT-58 kills trastuzumab-resistant breast cancer stem-like cells
N-terminal HSP90 inhibitors in development have had issues arising from heat shock response (HSR) induction and off-target effects. We sought to investigate the capacity of NCT-58, a rationally-synthesized C-t...
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Article
Open AccessA novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer
Trastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this target have had little s...
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Article
Open AccessDifferential Regulation of Gene Expression in Lung Cancer Cells by Diacyglycerol-Lactones and a Phorbol Ester Via Selective Activation of Protein Kinase C Isozymes
Despite our extensive knowledge on the biology of protein kinase C (PKC) and its involvement in disease, limited success has been attained in the generation of PKC isozyme-specific modulators acting via the C1...
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Article
Open AccessDevelopment of a novel Hsp90 inhibitor NCT-50 as a potential anticancer agent for the treatment of non-small cell lung cancer
Despite the development of advanced therapeutic regimens such as molecular targeted therapy and immunotherapy, the 5-year survival of patients with lung cancer is still less than 20%, suggesting the need to de...
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Article
Open AccessCurcumin interacts directly with the Cysteine 259 residue of STAT3 and induces apoptosis in H-Ras transformed human mammary epithelial cells
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is latent but constitutively activated in many types of cancers. It is well known that STAT3 plays a key role in inflam...
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Article
Hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retina is suppressed by HIF-1α destabilization by SH-1242 and SH-1280, novel hsp90 inhibitors
In diabetic retinopathy (DR), visual deterioration is related with retinal neovascularization and vascular hyperpermeability. Anti-vascular endothelial growth factor (VEGF) agents are currently utilized to sup...
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Article
Physiologically based pharmacokinetic modeling of SNU-0039, an anti-Alzheimer’s agent, in rats
The objective of this study was to characterize the systemic and tissue kinetics of 2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl) benzofuran (SNU-0039), an inhibitor of β-amyloid protein aggregation, in rats. Si...
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Article
Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies
The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1–TM6). TRPV1 is found in the central and peripheral n...
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Article
Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors
The transient receptor potential V1 channel (vanilloid receptor, TRPV1) represents a promising therapeutic target for inflammatory pain and other conditions involving C-fiber sensory afferent neurons. Sensitiv...
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Article
Design and synthesis of bioisosteres of ultrapotent protein kinase C (PKC) ligand, 5-Acetoxymethyl-5-hydroxymethyl-3-alkylidene tetrahydro-2-furanone
Three compounds, 5-(acetoxymethyl)-5-(hydroxymethyl)-3-tetradecyl-2,5-dihydro-2-furanone (3), 5-(acetoxymethyl)-5-(hydroxymethyl)-3,3-dihexyltetrahydro-2-furanone (4) and 5-(acetoxymethyl)-5-(hydroxymethyl)-3,3-d...
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Article
Synthesis and biological activity of 5-hydroxy-4-quinolones and 5-methoxy-4-quinolones as truncated acridones
A series of 5-hydroxy-4-quinolone (3) and 5-methoxy-4-quinolone (4) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor, antiherpes and antituberculosis activities. Among them...
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Article
Conformationally constrained analogues of diacylglycerol having a perhydrofuro[3,4-c]furan-1,4-dione bis-γ-butyrolactone skeleton
Bis-ψ-lactones (1, 2) having a perhydrofuro[3,4-c]furan-1,4-dione skeleton were designed as conformationally constrained diacylglycerol analogues. They were synthesized from D-apiose in 11 steps, and evaluated as...
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Article
Synthesis and antiviral activity of fluoro sugar nucleosides 2: Synthesis and biological evaluations of 2′, 3′-dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-D-arabinofuranosyl nucleosides
