Article
Biochemistry & Molecular Biology
Romain Hany, Jean-Philippe Leyris, Guillaume Bret, Sylvie Mallie, Chamroeun Sar, Maxime Thouaye, Abdallah Hamze, Olivier Provot, Pierre Sokoloff, Jean Valmier, Pascal Villa, Didier Rognan
Summary: This study identifies small molecular weight ligands that can inhibit the Fms-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase at the extracellular level. These ligands show strong inhibition in cell lines and a mouse model, demonstrating their potential as therapeutic inhibitors.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Zaid Anis Sherwani, Ruqaiya Khalil, Mohammad Nur-e-Alam, Sarfaraz Ahmed, Zaheer Ul-Haq
Summary: The study focused on designing inhibitors for the NMDA receptor, an important ionotropic receptor subtype in the brain, known for its roles in various neurological diseases. Through virtual screening techniques, potential NMDA inhibitor drugs were identified for further testing, indicating potential therapeutic value in treating neurological disorders.
MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Medve Laura, Gealageas Ronan, Lam Bao Vy, Guillaume Valentin, Castillo-Aguilera Omar, Camberlein Virgyl, Catherine Piveteau, Rosell Melissa, Fleau Charlotte, Warenghem Sandrine, Charton Julie, Dumont-Ryckembusch Julie, Bosc Damien, Leroux Florence, van Endert Peter, Deprez Benoit, Deprez-Poulain Rebecca
Summary: ERAP2 is an emerging pharmacological target in cancer immunotherapy and autoinflammatory disease control, and selective inhibitors and activators have been identified in this study, which could serve as useful starting points for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Benjamin Neveu, Chantal Richer, Pauline Cassart, Maxime Caron, Camille Jimenez-Cortes, Pascal St-Onge, Claire Fuchs, Nicolas Garnier, Stephane Gobeil, Daniel Sinnett
Summary: ETV6 transcriptional activity is crucial for blood cell development, but its regulatory network is still unknown. We identified genes that modulate ETV6 repressive transcriptional activity and revealed their role in cellular transformation.
Article
Multidisciplinary Sciences
Osha Roopnarine, Samantha L. Yuen, Andrew R. Thompson, Lauren N. Roelike, Robyn T. Rebbeck, Philip A. Bidwell, Courtney C. Aldrich, Razvan L. Cornea, David D. Thomas
Summary: In this study, FRET-based biosensors were used in live cells to screen small-molecules that can alter the structure and activity of SERCA2a, with the aim of discovering drug-like small-molecule activators for heart failure treatment. 50,000 compounds were screened, and 18 hit compounds were identified as SERCA modulators, with half being activators and half being inhibitors. Five promising SERCA activators were identified, one of which showed improved Ca2+-transport activity compared to Ca2+-ATPase activity. These findings provide a foundation for future testing and lead development for heart failure therapy.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Qingtong Zhou, Wanjing Guo, Antao Dai, Xiaoqing Cai, Marton Vass, Chris de Graaf, Wenqing Shui, Suwen Zhao, Dehua Yang, Ming-Wei Wang
Summary: Allosteric modulators offer pharmacological advantages by affecting downstream signaling without competing for orthosteric sites. Computational approaches were used to identify allosteric modulators targeting GLP-1R, resulting in the discovery of negative and positive modulators through structure-based and ligand-based virtual screening methods, respectively. This computational approach may be applicable for discovering allosteric modulators of other GPCRs.
Article
Neurosciences
Mohammad Qneibi, Mohammad Hawash, Nidal Jaradat, Sosana Bdir
Summary: Background: Glutamatergic synapses mediate excitatory neurotransmission in the CNS. Objective: To investigate the modulating effect of different compounds on AMPA receptors. Methods: Patch-clamp electrophysiology was performed on HEK293T recombinant AMPAR subunits. Results: The results showed that BDZ derivatives acted as negative modulators on AMPARs, particularly BDZs (8, 9, and 15), which increased desensitization rate and delayed deactivation process. Conclusion: BDZ compounds can act as negative allosteric AMPAR modulators to restore glutamatergic synaptic transmission, with neuroprotective properties.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
AyoOluwa O. Aderibigbe, Pankaj Pandey, Robert J. Doerksen
Summary: The study compared computational predictions with experimental results of the ternary CB1 complex structure and the binding mode of the negative allosteric modulator at different sites on the receptor.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Bruno Cruz de Souza, Pedro Sousa Lacerda, Samuel Silva da Rocha Pita, Rodrigo Bentes Kato, Franco Henrique Andrade Leite
Summary: This study investigates the etiology of visceral Leishmaniasis, treatment limitations, and potential drug screening based on the 3D structural of biological targets.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Medicinal
Gyorgy Szabo, Oliver Elias, Peter Erdelyi, Attila Potor, Gyorgy I. . Turos, Benedek I. Karolyi, Gabor Varro, Agnes Gy. Vasko, Imre Bata, Gabor L. Kapus, Zoltan Dohanyos, Amrita A. . Bobok, Laszlo Fodor, Marta Than, Monika Vastag, Zsolt Komlodi, Soukupne Rita E. Kedves, Eva Mako, Brigitta Suveges, Greiner Istvan
Summary: This study discloses the discovery and characterization of novel naphthyridine derivatives with selective alpha 5-GABA(A)R negative allosteric modulator (NAM) activity. By utilizing a scaffold-hopping strategy, fused [6 + 6] bicyclic scaffolds were designed and synthesized. Among these, 1,6-naphthyridinones were identified as potent and selective alpha 5-GABA(A)R NAMs with improved profile. Compound 20, with the most balanced profile, demonstrated in vivo proof of concept (POC) for the new scaffold in animal models of cognitive impairment associated with schizophrenia (CIAS).
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jiayin Diao, Maggie Lam, Karen J. Gregory, Katie Leach, Jane E. Bourke
Summary: Asthma is a heterogeneous chronic airway disease with a need for improved therapeutics. The calcium-sensing receptor (CaSR) is upregulated in asthma and its agonist, spermine, contributes to bronchoconstriction. Negative allosteric modulators (NAMs) of CaSR have shown to inhibit inflammation and hyperresponsiveness in asthma models, but their effectiveness as bronchodilators compared to standard care is not yet established. This study demonstrates that different classes of CaSR NAMs can inhibit spermine-induced CaSR signaling and reverse airway contraction. CaSR NAMs also maintain their bronchodilator effects under conditions of beta(2)-adrenergic receptor desensitization. These findings support CaSR as a potential drug target and NAMs as alternative bronchodilators in asthma.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jay Rollins, Tyler Worthington, Allison Dransfield, Jordan Whitney, Jordan Stanford, Emily Hooke, Joseph Hobson, Jacob Wengler, Sandra Hope, Dario Mizrachi
Summary: Cell-adhesion molecules (CAMs) are responsible for various cell interactions. In this study, the expression of CLDN proteins in E. coli is investigated and its consequences are discussed. The iCLASP method is introduced as a high-throughput screening approach for identifying paracellular modulators for CLDN2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Jana Deitersen, Lena Berning, Fabian Stuhldreier, Sara Ceccacci, David Schluetermann, Annabelle Friedrich, Wenxian Wu, Yadong Sun, Philip Boehler, Niklas Berleth, Maria Jose Mendiburo, Sabine Seggewiss, Ruchika Anand, Andreas S. Reichert, Maria Chiara Monti, Peter Proksch, Bjoern Stork
Summary: High-throughput screening identified arzanol as a novel autophagy-modulating drug that not only induces early autophagosome biogenesis but also inhibits later autophagy events. Arzanol sensitizes bladder cancer cells to cisplatin and induces mitochondrial fragmentation, suggesting its potential as a lead compound for cancer therapy. The compound targets proteins related to mitochondria-associated quinone-binding oxidoreductases, making it a valuable tool for autophagy research.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Physical
Shuo Wang, Lei Li, Kwan San Hui, Duc Anh Dinh, Zhiyi Lu, Qiuju Zhang, Kwun Nam Hui
Summary: Electrochemical nitrate reduction reaction (NO3RR) has potential in wastewater management and carbon-neutral ammonia synthesis, but lacks high-quality catalysts with controllable reaction pathways and high activity and selectivity. In this study, we explore the application of single atom alloys (SAAs) in nitrate reduction through high-throughput first-principles calculations. We identify Ni/Cu(111) as the most active SAA catalyst for NO3RR and find that the adsorption free energy of *NO3 can serve as an efficient descriptor to design and predict the NO3RR performance of SAAs. Furthermore, we reveal the pH-dependent properties of Cu-based SAAs, which influence the competition between the hydrogen evolution reaction (HER) and NO3RR.
Review
Biochemistry & Molecular Biology
Clara Blanes-Mira, Pilar Fernandez-Aguado, Jorge De Andres-Lopez, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel, Gregorio Fernandez-Ballester
Summary: The rapid advances in 3D techniques and computational methods have led to the identification of highly active compounds in computer drug design. Molecular docking is widely used in virtual screening to filter potential ligands targeted to proteins. Consensus scoring methods improve virtual screening outcomes by averaging the rank or score of individual molecules obtained from different docking programs.
Article
Chemistry, Organic
Areum Jung, Sun-Joon Min
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Juhyeon Kim, Yoon Jung Kim, Ashwini M. Londhe, Ae Nim Pae, Hyunah Choo, Hak Joong Kim, Sun-Joon Min
Article
Biochemistry & Molecular Biology
Juhyeon Kim, Yihoon Kim, Ahmed Z. Abdelazem, Hak Joong Kim, Hyunah Choo, Hoon Seok Kim, Jung Ok Kim, Yeon-Joon Park, Sun-Joon Min
BIOORGANIC CHEMISTRY
(2020)
Article
Microbiology
Hoon Seok Kim, Jung Ok Kim, Ji Eun Lee, Kang Gyun Park, Hae Kyung Lee, Soo-Young Kim, Sun-Joon Min, Juhyeon Kim, Yeon-Joon Park
JOURNAL OF CLINICAL MICROBIOLOGY
(2020)
Article
Multidisciplinary Sciences
Ye-Ram Kim, Jae-Sung Kim, Su-Jin Gu, Sungsin Jo, Sojin Kim, Sun Young Kim, Daeun Lee, Kiseok Jang, Hyunah Choo, Tae-Hwan Kim, Jae U. Jung, Sun-Joon Min, Chul-Su Yang
SCIENTIFIC REPORTS
(2020)
Article
Biochemical Research Methods
MiJung Park, Yeon-Joon Park, Jinkyung Yu, Jieun Lee, Dae-Ro Ahn, Sun-Joon Min
JOURNAL OF MICROBIOLOGICAL METHODS
(2020)
Article
Chemistry, Multidisciplinary
Sangwoon Park, Seungri Yoon, Sun-Joon Min
BULLETIN OF THE KOREAN CHEMICAL SOCIETY
(2021)
Article
Nanoscience & Nanotechnology
Jiwon Kim, Donghyuk Jo, Seung-Hyun Yang, Chan-Gyu Joo, Nicholas Whiting, Shivanand Pudakalakatti, Hyeonglim Seo, Hye Young Son, Sun-Joon Min, Pratip Bhattacharya, Yong-Min Huh, Jeong Hyun Shim, Youngbok Lee
Summary: This study developed a synthetic method for partially Si-29-enriched porous silicon nanoparticles and examined their usability in hyperpolarized Si-29 MRI agents, demonstrating higher signal enhancement than naturally abundant samples. The findings suggest potential applications of Si-29-enriched porous silicon nanoparticles as drug delivery vehicles and theragnostic platforms in the future.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Medicinal
Daeun Lee, Eunbi Lee, Sein Jang, Kyungmin Kim, Euni Cho, Seok-Jun Mun, Wooic Son, Hye-In Jeon, Hyo Keun Kim, Young Jin Jeong, Yuno Lee, Ji Eun Oh, Hye Hyun Yoo, Youngbok Lee, Sun-Joon Min, Chul-Su Yang
Summary: The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis interacts with SNX9 to inhibit endosome trafficking and suppress TLR4 inflammatory signaling. A small molecule called DATPT, derived from Rv3364c, shows potent anti-inflammatory and antibacterial activities in vitro and in vivo, and demonstrates significant therapeutic effects in a mouse model of sepsis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jae-Sung Kim, Ye-Ram Kim, Sein Jang, Sang Geon Wang, Euni Cho, Seok-Jun Mun, Hye-In Jeon, Hyo-Keun Kim, Sun-Joon Min, Chul-Su Yang
Summary: Rubicon interacts with p22phox to regulate ROS production in immune cells. Mito-TIPTP inhibits the interaction between Rubicon and p22phox, enhancing mitochondrial function and showing therapeutic effects in colitis models. This suggests Mito-TIPTP as a potential therapeutic agent for colitis by targeting the Rubicon-p22phox interaction.
Article
Nanoscience & Nanotechnology
Seungbeom Park, Woomin Park, Kangjoo Lee, Sun-Joon Min, Kwang-Suk Jang
Summary: A network structure of solar-thermal materials has been developed for zero energy heating of a solvent under 1 sun illumination, which successfully accelerated catalytic reactions. The network structure material exhibited excellent sunlight absorption properties, reduced heat loss, increased reaction solution temperature, and demonstrated easy and low-energy-consuming multicycle use.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Sun-Joon Min, Sunhwa Jung, Seungri Yoon, Jae Kyun Lee
Summary: This study achieved the stereoselective synthesis of C-4-substituted benzo[a]-quinolizidines through redox-controlled catalytic C-C-bond-forming reactions. The allylation of N-Cbz tetrahydroisoquinolines was efficiently catalyzed by aerobic DDQ, and the resulting alpha-allylated products were transformed to enones through cross-metathesis reactions. Finally, palladium-catalyzed hydrogenation led to the reduction of the alkene, removal of protecting groups, and intramolecular reductive amination in one step, resulting in the desired benzo[a]quinolizidines as single diastereomers.
Article
Materials Science, Biomaterials
Jaewoon Lee, Jeunghwan Kim, Incheol Heo, Su Jin Kim, Sein Jang, Ho-Young Lee, Kwang-Suk Jang, Chul-Su Yang, Youngbok Lee, Won Cheol Yoo, Sun-Joon Min
Summary: Covalent conjugation of bifunctional silica nanoparticles (SNPs) was synthesized and applied for in vivo multimodal imaging. The bifunctional SNPs exhibited prolonged circulation in mice, facilitating systemic drug delivery.
BIOMATERIALS SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yu Jin Hwang, Seung Jae Hyeon, Younghee Kim, Sungsu Lim, Min Young Lee, Jieun Kim, Ashwini M. Londhe, Lizaveta Gotina, Yunha Kim, Ae Nim Pae, Yong Seo Cho, Jihye Seong, Hyemyung Seo, Yun Kyung Kim, Hyunah Choo, Hoon Ryu, Sun-Joon Min
Summary: This study demonstrates the potential therapeutic effects of a novel SETDB1 inhibitor, APQ, in improving symptoms and function in HD mouse models by modulating H3K9me3 levels. In vitro and in vivo experiments support the promising role of APQ in treating HD through epigenetic regulation.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Materials Science, Biomaterials
Jeong Yi Kang, Seulgi Kim, Juhyeon Kim, Nae-Gyu Kang, Chul-Su Yang, Sun-Joon Min, Jin Woong Kim
Summary: The study presents an intracellular delivery approach utilizing cell-penetrating peptide (CPP)-conjugated lipid/polymer hybrid nanovehicles (LPNVs) for ER-targeting, showing efficient uptake by cells and specific ER-targeting ability. Remarkable lysosomal escape of the LPNVs was observed due to effective pH buffering with the aid of PEO-b-PCL-b-PEO, indicating the potential of the LPNVPnt system for elaborate drug delivery technology development at the intracellular level.
JOURNAL OF MATERIALS CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Ali Mehri, Karim Mahnam, Hajar Sirous, Mahmoud Aghaei, Leila Rafiei, Mahboubeh Rostami
Summary: One potential approach for tumor therapy is inhibiting the binding between MDM2 and p53 to reactivate p53 in tumor cells. In this study, Monastrol derivatives were designed as MDM2 inhibitors and evaluated for their cytotoxicity on cancer cells. Compound 5d showed the best inhibitory results in silico and in vitro experiments. These findings suggest that Monastrol derivatives have the potential to be candidates for MDM2 inhibition.
CHEMICAL BIOLOGY & DRUG DESIGN
(2024)