A5027714559- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Drug Transport and Resistance Mechanisms
- Lung Cancer Treatments and Mutations
- Computational Drug Discovery Methods
- Click Chemistry and Applications
- Lung Cancer Research Studies
- Cancer Mechanisms and Therapy
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Cancer, Hypoxia, and Metabolism
- Quinazolinone synthesis and applications
- Metabolomics and Mass Spectrometry Studies
- Pharmacogenetics and Drug Metabolism
- Antibiotics Pharmacokinetics and Efficacy
- Synthesis and Biological Evaluation
- Pesticide Exposure and Toxicity
- Multiple Myeloma Research and Treatments
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Amino Acid Enzymes and Metabolism
- Graphene and Nanomaterials Applications
- Tryptophan and brain disorders
- Angiogenesis and VEGF in Cancer
- Environmental Toxicology and Ecotoxicology
Korea Research Institute of Chemical Technology
2015-2024
Korea University of Science and Technology
2015-2023
GTx (United States)
2010-2014
Seoul National University
2008-2012
The Ohio State University
2008-2011
University of Tennessee Health Science Center
2010
University of Tennessee at Knoxville
2010
Identification of blood-brain barrier (BBB) permeability a compound is major challenge in neurotherapeutic drug discovery. Conventional approaches for BBB measurement are expensive, time-consuming and labor-intensive. associated with diverse chemical properties compounds. However, prediction models have been developed using small datasets limited features, which usually not practical due to their low coverage diversity Aim this study develop model large dataset applications. This can be used...
Novel ABI-III compounds were designed and synthesized based on our previously reported ABI-I ABI-II analogues. are highly potent against a panel of melanoma prostate cancer cell lines, with the best compound having an average IC50 value 3.8 nM. They not substrate Pgp thus may effectively overcome Pgp-mediated multidrug resistance. analogues maintain their mechanisms action by inhibition tubulin polymerization.
To block the metabolically labile sites of novel tubulin inhibitors targeting colchicine binding site based on SMART, ABI, and PAT templates, we have designed, synthesized, biologically tested three focused sets new derivatives with modifications at carbonyl linker, para-position in C ring SMART template, modification A template. Structure-activity relationships these compounds led to identification benzimidazole imidazo[4,5-c]pyridine-fused represented by 4 7, respectively, which showed...
Introduction The androgen receptor (AR) is the most highly expressed steroid in breast cancer with 75–95% of estrogen (ER)-positive and 40–70% ER-negative cancers expressing AR. Though historically were treated steroidal androgens, their use fell from favor because virilizing side effects emergence tamoxifen. Nonsteroidal, tissue selective modulators (SARMs) may provide a novel targeted approach to exploit therapeutic benefits therapy cancer. Materials Methods Since MDA-MB-453...
A series of 4-aryl-2-benzoyl-imidazoles were designed and synthesized based on our previously reported 2-aryl-4-benzoyl-imidazole (ABI) derivatives. The new structures reversed the aryl group benzoyl previous ABI named as reverse (RABI) analogues. RABIs evaluated for biological activity against eight cancer cell lines including multidrug-resistant lines. In vitro assays indicated that several RABI compounds had excellent antiproliferative properties, with IC50 values in low nanomolar range....
The objective of this study was to evaluate the permeability small molecules into brain via blood–brain barrier in zebrafish and investigate possibility using animal model as a screening tool during early stages drug discovery. Fifteen compounds were used understand permeation mice. ratio brain-to-plasma concentration compared between two models. partition coefficient (Kp,brain), estimated at designated times (0.167, 0.25, 0.5, or 2 h) after oral administrations (per os, p.o), ranged from...
Sensory abnormalities are observed in ~90% of individuals with autism spectrum disorders (ASD), but the underlying mechanisms poorly understood. GluN2B, an NMDA receptor subunit that regulates long-term depression and circuit refinement during brain development, has been strongly implicated ASD, whether GRIN2B mutations lead to sensory remains unclear. Here, we report Grin2b-mutant mice show behavioral hypersensitivity hyperconnectivity associated anterior cingulate cortex (ACC). a...
Background Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms cancer. When administered with pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited striking activity patients refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated inter-individual variability pharmacokinetics and outcomes therapy. Methodology/Principal Findings Thirty-five who received...
Abstract Proteolysis targeting chimeras (PROTACs) are an emerging strategy for promoting targeted protein degradation by inducing the proximity between proteins and E3 ubiquitin ligases. Although successful of numerous PROTACs has been demonstrated, elements that determine degradability PROTAC-targeted have not yet explored. In this study, we developed von Hippel-Lindau-Cereblon (VHL-CRBN) heterodimerizing induce CRBN, but VHL. A quantitative proteomic analysis further revealed VHL-CRBN...
// Vijayendra Agrawal 1 , Sony Maharjan Kyeojin Kim 2 Nam-Jung 3 Jimin Son Keunho Lee Hyun-Jung Choi Seung-Sik Rho Sunjoo Ahn 4 Moo-Ho Won 5 Sang-Jun Ha Gou Young Koh 6 Young-Myeong 7 Young-Ger Suh and Young-Guen Kwon Department of Biochemistry, College Life Science Biotechnology, Yonsei University, Seoul 120-749, Republic Korea, Pharmacy, National 599 Gwanak-ro, Gwanak-gu, 151-742, Kyung Hee 130-701, Korea Research Institute Chemical Technology (KRICT), 141 Gajeong-ro, Yuseong-gu, Daejeon...
Poor metabolic stability leads to drug development failure. Therefore, it is essential evaluate the of small compounds for successful discovery and development. However, evaluating in vitro vivo expensive, time-consuming laborious. In addition, only a few free software programs are available data prediction. this study, we aimed develop prediction model that predicts compounds.We developed computational model, PredMS, which as stable or unstable human liver microsomes. PredMS based on random...
Formation of microtubules is a dynamic process that involves polymerization and depolymerization αβ-tubulin heterodimers. Drugs enhance or inhibit tubulin can destroy this process, arresting cells in the G(2)/M phase cell cycle. Although drugs target generally demonstrate cytotoxic potency subnanomolar range, resistance due to drug efflux common phenomenon among antitubulin agents. We recently reported class 4-substituted methoxybenzoyl-aryl-thiazoles (SMART) exhibited great vitro broad...
Microtubules are critical components of the cytoskeleton. Perturbing their function arrests growth a broad spectrum cancer cell lines, making microtubules an excellent and established target for chemotherapy. All U.S. Food Drug Administration-approved antitubulin agents bind to paclitaxel or vinblastine binding sites in tubulin. Because complexity structures, it is difficult structurally modify vinca alkaloids taxanes develop orally bioavailable agents. Antitubulin that colchicine-binding...
The human rhinovirus (hRV) is the causative agent of common cold that often aggravates respiratory complications in patients with asthma or chronic obstructive pulmonary disease. high rate mutations and variety serotypes are limiting development anti-hRV drugs, which emphasizes need for discovery novel lead compounds. Previously, we identified antiviral compound 1 used here as starting material developing a series efficacy against hRV-A -B. Improved metabolic stability was achieved by...
Abstract Autism spectrum disorder is characterized by early postnatal symptoms, although little known about the mechanistic deviations that produce them and whether correcting has long-lasting preventive effects on adult-stage deficits. ARID1B, a chromatin remodeler implicated in neurodevelopmental disorders, including autism disorder, exhibits strong embryonic- postnatal-stage expression. We report here Arid1b -happloinsufficient ( +/– ) mice display autistic-like behaviors at juvenile...
Abstract Tubulin is an attractive and established target for anticancer therapy. To date, the only method to determine binding of inhibitor tubulin has been competitive radioligand assays. We developed a non‐radioactive mass spectrometry (MS) assay study colchicine, vinblastine paclitaxel identify which these three sites that novel binds. The involves very simple step separating unbound ligand from macromolecules using ultrafiltration. in filtrate can be accurately determined highly...