Review
Urology & Nephrology
Aude Servais, Kay Thomas, Luca Dello Strologo, John A. Sayer, Soumeya Bekri, Aurelia Bertholet-Thomas, Matthew Bultitude, Giovanna Capolongo, Rimante Cerkauskiene, Michel Daudon, Steeve Doizi, Valentine Gillion, Silvia Gracia-Garcia, Jan Halbritter, Laurence Heidet, Marleen van den Heijkant, Sandrine Lemoine, Bertrand Knebelmann, Francesco Emma, Elena Levtchenko
Summary: Cystinuria is a genetic disorder characterized by high urinary cystine excretion leading to stone formation. Clinical practice recommendations for diagnosis, treatment, and follow-up were developed from June 2018 to December 2019. The guidance covers various aspects of management for both adults and children with cystinuria.
KIDNEY INTERNATIONAL
(2021)
Review
Urology & Nephrology
Nirmal Prasad Bhatt, Aniruddh Vijay Deshpande, Malcolm Ronald Starkey
Summary: Cystinuria is a rare genetic kidney stone disease with no cure. This systematic review evaluated the available literature on non-surgical interventions for cystinuria. The results suggest that first-line therapies such as high diuresis and urinary alkalinization can reduce urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding drugs further reduces cystine stone formation and recurrence. Combined intervention with alkalinizing agents and cystine-binding drugs synergistically reduces stone recurrence.
JOURNAL OF NEPHROLOGY
(2023)
Review
Agriculture, Dairy & Animal Science
Simona Kovarikova, Petr Marsalek, Katerina Vrbova
Summary: Cystinuria is a metabolic disorder affecting dogs and cats, leading to potential urethral stones. Mutation in genes and the mode of inheritance causing cystinuria have been identified in only some canine breeds.
Article
Biochemistry & Molecular Biology
Clara Mayayo-Vallverdu, Miguel Lopez de Heredia, Esther Prat, Laura Gonzalez, Meritxell Espino Guarch, Clara Vilches, Lourdes Munoz, Miguel A. Asensi, Carmen Serra, Amadeu Llebaria, Mercedes Casado, Rafael Artuch, Gloria Garrabou, Pablo M. Garcia-Roves, Federico V. Pallardo, Virginia Nunes
Summary: The high recurrence rate of cystine lithiasis in cystinuria patients calls for new therapeutic options. Antioxidant defect has been observed in cystinuria, leading to testing of antioxidant molecules as new treatments. In this study, L-Ergothioneine was found to decrease stone formation rate by over 60% and delay onset of calculi in a mouse model.
Article
Urology & Nephrology
Hannah Warren, Daniel Poon, Rohit Srinivasan, Kerushan Thomas, Giles Rottenberg, Matthew Bultitude, Kay Thomas
Summary: Cystine stones are commonly perceived as hard and difficult to treat. This study found that cystine stones in cystinuria patients have a low mean Hounsfield Unit (HU), indicating they are hard to treat. Additionally, there was no significant difference in mean HU between different genotypes (SLC3A1 and SLC7A9), with HU correlating with stone size.
WORLD JOURNAL OF UROLOGY
(2021)
Editorial Material
Urology & Nephrology
Valentine Gillion, Thibaud-Pierre Saussez, Sandy Van Nieuwenhove, Michel Jadoul
Summary: Cystinuria is a genetic disease characterized by recurrent kidney stones. Prevention strategies include diluting and alkalinizing urine, avoiding excessive intake of methionine, and avoiding foods rich in cystine. Patients and physicians should be aware of the potential harm of dietary supplements containing cystine and methionine for individuals with cystinuria.
CLINICAL KIDNEY JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Alexander G. Shtukenberg, Longqin Hu, Amrik Sahota, Bart Kahr, Michael D. Ward
Summary: Aberrant crystallization in the human body can lead to various diseases, including kidney stones. Understanding the fundamental stages of stone formation and developing rational treatments remain challenges. Studies on L-cystine kidney stones have revealed complex crystal growth mechanisms and potential therapeutic pathways.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Agriculture, Dairy & Animal Science
Therese Fitzwilliams, Julie L. L. Wolff-Sneedorff, Merete Fredholm, Peter Karlskov-Mortensen, Bernt Guldbrandtsen, Camilla S. S. Bruun
Summary: Cystinuria is a genetic disease that can lead to cystine urolith formation and the English bulldog is the most commonly affected breed. This study investigated the occurrence of three mutations associated with cystinuria in the Danish population of English bulldogs and found a significant association between the c.568A>G and c.2086A>G mutations and cystinuria in male English bulldogs.
Article
Genetics & Heredity
Lexin Liu, Zihao Xu, Yuelin Guan, Ying Zhang, Xue Li, Yunqing Ren, Lidan Hu, Xiang Yan
Summary: This study presents the genotypic and phenotypic characteristics of a unique case in a three-generation Chinese family with cystinuria. The patient suffered from severe urolithiasis and renal damage, with stones mainly composed of cystine. The analysis identified two novel compound heterozygous mutations of the SLC3A1 gene in the patient. The findings expand the understanding of SLC3A1 and highlight the importance of genetic screening in clinical practice.
Article
Chemistry, Physical
Uekriye cakmak
Summary: Novel diamides were synthesized and characterized using various spectroscopic techniques. In vitro experiments showed that compound IV exhibited the strongest urease inhibition activity and molecular docking studies confirmed its binding to the active site of the target enzyme. Additionally, compound I showed the highest antioxidant activity and compound III demonstrated superior antimicrobial activity against bacteria B. cereus. These diamides have potential applications in the pharmaceutical industry.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Review
Urology & Nephrology
Fatima Tokhmafshan, Paul R. Goodyer
Summary: This study reviews the natural history of cystinuria in presymptomatic children and finds that each new stone is preceded by 6-12 months of urine specific gravity of more than 1.020. Although urine specific gravity and pH are not different in stone formers vs. nonstone formers, other unknown factors may be the strongest determinants of individual risk.
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
(2023)
Article
Pediatrics
Juan Alberto Pinero-Fernandez, Carmen Vicente-Calderon, Maria Jose Lorente-Sanchez, Maria Jesus Juan-Fita, Jose Maria Egea-Mellado, Inmaculada C. Gonzalez-Gallego
Summary: This study provides a phenotypic characterization of pediatric patients with cystinuria and shows that neonatal screening can be a useful strategy for early detection and prevention of the disease.
PEDIATRIC NEPHROLOGY
(2023)
Article
Health Care Sciences & Services
Sarah M. Azer, David S. Goldfarb
Summary: Cystinuria is a common genetic cause of recurrent kidney stones. It is characterized by increased levels of cystine in the urine, resulting in recurrent kidney stones. Managing cystinuria mainly focuses on stone prevention.
Article
Biochemistry & Molecular Biology
Miguel Lopez de Heredia, Lourdes Munoz, Ciriaco Carru, Salvatore Sotgia, Angelo Zinellu, Carmen Serra, Amadeu Llebaria, Yukio Kato, Virginia Nunes
Summary: Cystinuria is a rare inherited disorder characterized by hyperexcretion of certain amino acids, leading to cystine stone formation in the urinary tract. Study analyzing levels of S-methyl-L-ergothioneine in urine showed potential as a biomarker for discriminating between different cystinuria phenotypes based on age, gender, and stone formation characteristics. Improved management of cystinuria patients could be achieved through monitoring this urinary biomarker.
Review
Urology & Nephrology
Harun Ucmak, Mehmet Giray Sonmez, Selcuk Guven
Summary: In the dietary management of cystine stone formers, considerations should be given to urine alkalization and hydration therapy, and a vegetarian diet is particularly suitable for the treatment of cystine stone disease. Personalized medical therapy, including alkalinization and cystine-binding drugs, is crucial in preventing chronic kidney disease and kidney failure in cystinuria.
WORLD JOURNAL OF UROLOGY
(2023)
Review
Chemistry, Medicinal
Sumi Lee, Longqin Hu
MEDICINAL CHEMISTRY RESEARCH
(2020)
Article
Chemistry, Medicinal
Herve Aloysius, Longqin Hu
MEDICINAL CHEMISTRY RESEARCH
(2020)
Article
Chemistry, Medicinal
Herve Aloysius, Longqin Hu
MEDICINAL CHEMISTRY RESEARCH
(2020)
Biographical-Item
Chemistry, Medicinal
Siming L. Wang, Longqin Hu, Binghe Wang
MEDICINAL CHEMISTRY RESEARCH
(2020)
Article
Biochemical Research Methods
Sumi Lee, Dhulfiqar Ali Abed, Lesa J. Beamer, Longqin Hu
Summary: This study optimized the detection of inhibitors of Keap1-Nrf2 protein-protein interaction (PPI) using a TR-FRET assay, demonstrating its potential for high-throughput screening and lead optimization.
Article
Chemistry, Medicinal
Ashwini Sadanand Ranade, Joseph R. Bertino, Longqin Hu
Summary: 5'-Methylthioadenosine (MTA) is a natural substrate converted to adenine via a salvage pathway for AMP production in normal healthy cells. A series of carbamate prodrugs of MTA was designed and evaluated for potential targeted therapy against tumor cells. These prodrugs were stable in phosphate buffer and activated to MTA in the presence of mouse liver microsomes.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Dhulfiqar Ali Abed, Sumi Lee, Xia Wen, Ahmed R. Ali, Vaibhav Mangipudy, Lauren M. Aleksunes, Longqin Hu
Summary: A series of novel compounds were designed to investigate the protein-protein interaction between Keap1 and Nrf2, with compound 7q showing significant activation of the cellular Nrf2 signaling pathway and suppression of pro-inflammatory cytokines, indicating potential therapeutic application for neuroinflammatory disorders.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Editorial Material
Chemistry, Medicinal
Moorthy S. S. Palanki, Michael S. Wolfe, Longqin Hu
MEDICINAL CHEMISTRY RESEARCH
(2021)
Review
Chemistry, Multidisciplinary
Alexander G. Shtukenberg, Longqin Hu, Amrik Sahota, Bart Kahr, Michael D. Ward
Summary: Aberrant crystallization in the human body can lead to various diseases, including kidney stones. Understanding the fundamental stages of stone formation and developing rational treatments remain challenges. Studies on L-cystine kidney stones have revealed complex crystal growth mechanisms and potential therapeutic pathways.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Sumi Lee, Dhulfiqar Ali Abed, Mai-Uyen Nguyen, Michael P. Verzi, Longqin Hu
Summary: The Keap1-Nrf2-ARE pathway is important in responding to oxidative stress. Small molecule inhibitors targeting the Keap1-Nrf2 protein-protein interaction (PPI) can be potential agents for chronic inflammatory diseases. Compound 12d with a 2-(4-fluorobenzyloxy) group was identified as the most potent inhibitor of Keap1-Nrf2 PPI. It showed increased mRNA levels of downstream genes through Nrf2 activation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jeffrey Yang, Subhadwip Basu, Longqin Hu
Summary: Small-molecule inhibitors targeting the PD-1/PD-L1 immune checkpoint axis are being explored as potential alternative therapies. In this study, a series of new derivatives were designed and evaluated for their inhibitory activity against the PD-1/PD-L1 protein-protein interaction. The inhibitors with specific appendages showed improved activity.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Review
Chemistry, Medicinal
Jun Wang, Daniel Lam, Jeffrey Yang, Longqin Hu
Summary: EGFR mutations can cause non-small cell lung cancer, and EGFR ex20ins mutations play a key role in oncogenesis. Mobocertinib, a novel small molecule therapeutic, has high anticancer potency against EGFR ex20ins-positive lung cancer and specificity to tumors that are resistant to other EGFR TKIs. The discovery of mobocertinib from osimertinib highlights the power of structure-based drug design and precision medicine approaches in the treatment of molecularly defined tumors.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Dhulfiqar Ali Abed, Ahmed R. Ali, Sumi Lee, Mai-Uyen Nguyen, Michael P. Verzi, Longqin Hu
Summary: Direct inhibition of the PPI between Keap1 and Nrf2 leads to Nrf2 accumulation and nuclear translocation, activating antioxidant response genes. A series of 1,4-bis(arylsulfonamido)naphthalene-N,N'-diacetic acid analogs were tested for Keap1-binding activity, with compound 24a showing the strongest binding affinity. In addition, compounds 12b, 15, and 24a were found to activate the Nrf2 pathway in NCM460D cells, increasing mRNA levels of GSTM3, HMOX1, and NQO1.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jeffrey Yang, Haifa Albanyan, Yiling Wang, Yanhui Yang, Amrik Sahota, Longqin Hu
Summary: Kidney stone diseases have a growing prevalence globally, calling for the development of new therapies to prevent stone formation. One approach to achieving this is the development of small molecule inhibitors that disrupt the crystallization process of stone-forming substances. A convenient assay platform has been established to evaluate the potential inhibitors and rank them for further study in preventing kidney stones.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Maryam Alapa, Chuanlong Cui, Ping Shu, Hong Li, Vlad Kholodovych, Annie Beuve
Summary: The study found that redox modifications play a crucial role in NO activation of GC1, with NO-stimulated GC1 containing more bound Cys, potentially disulfide bonds. Mass spectrometry identified ten oxidized and two reduced Cys in NO-stimulated GC1, and computational modeling narrowed down potential Cys candidates involved in disulfide bonds to Cys489 and Cys571. Mutational studies confirmed the involvement of Cys489 and Cys571 in GC1's response to NO, potentially as a thiol/disulfide switch.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
