Article
Cell Biology
Jeeyoung Lee, Soumyadeep Dey, Praveen K. Rajvanshi, Randall K. Merling, Ruifeng Teng, Heather M. Rogers, Constance T. Noguchi
Summary: Erythropoietin (EPO) is produced in the kidney in response to hypoxia and is essential for red blood cell production. In addition to its role in erythropoiesis, EPO also increases the production of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) in non-erythroid tissue, which improves oxygen delivery. This study found that during erythroid differentiation, EPO induces neuronal nitric oxide synthase (nNOS) and that nNOS is required for a normal erythropoietic response.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Maryam Akhtar, Jiabin Niu, Yujie Zhu, Zhaoyi Luo, Ting Tian, Yuanliang Dong, Yuan Wang, Muhammad Subaan Fareed, Li Lin
Summary: In this study, a combination of design, synthesis, computational study, in-vitro screening, and in-vivo evaluation was used to accelerate the discovery of anti-inflammatory drugs. The newly synthesized compounds exhibited strong dose-dependent inhibitory effects on nitric oxide (NO) release, with no obvious cytotoxicity. Several model compounds (7a, 7b, 7d, 7f, and 7g) showed promising anti-inflammatory activity in the in-vitro assay, with IC50 values ranging from 20.76 mu M to 47.8 mu M. Furthermore, these compounds demonstrated inhibition of ear edema in mice, indicating their potential as anti-inflammatory agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Kundan Solanki, Sajjan Rajpoot, Evgeny E. Bezsonov, Alexander N. Orekhov, Rohit Saluja, Anita Wary, Cassondra Axen, Kishore Wary, Mirza S. Baig
Summary: This article discusses the importance of nitric oxide synthases 1 (NOS1) and its byproduct nitric oxide (NO) in different tissues and diseases, highlighting the significance of understanding NOS1-derived NO signaling and identification of NO-metabolites for disease diagnosis and prognosis.
Article
Peripheral Vascular Disease
Jie Zhang, Ximing Wang, Yu Cui, Shan Jiang, Jin Wei, Jenna Chan, Anish Thalakola, Thanh Le, Lan Xu, Liang Zhao, Lei Wang, Kun Jiang, Feng Cheng, Trushar Patel, Jacentha Buggs, Volker Vallon, Ruisheng Liu
Summary: This study investigates the mechanism of hypertension in patients with diabetes and suggests that in early diabetes, upregulation of NOS1 in the macula densa plays a role in inhibiting TGF and increasing glomerular filtration rate, which helps in maintaining normal blood pressure.
Article
Cardiac & Cardiovascular Systems
Kevin O'Gallagher, Francesca Puledda, Owen O'Daly, Matthew Ryan, Luke Dancy, Philip J. Chowienczyk, Fernando Zelaya, Peter J. Goadsby, Ajay M. Shah
Summary: This study reveals the fundamental physiological role of nNOS in regulating cerebral blood flow and functional connectivity in the human hippocampus.
CARDIOVASCULAR RESEARCH
(2022)
Article
Nutrition & Dietetics
Ping Wang, Fan-Zhi Kong, Xiao-Hong Hong, Li Zhang, Wan-Hong Zhao, Jin-Cui Yang, Heng Zhang
Summary: A high shortening diet may contribute to obesity and depressive behaviors, which are regulated by neuronal nitric oxide synthase (nNOS).
Article
Cardiac & Cardiovascular Systems
Somy Yoon, Mira Kim, Hangyeol Lee, Gaeun Kang, Kenneth Bedi, Kenneth B. Margulies, Rajan Jain, Kwang-Il Nam, Hyun Kook, Gwang Hyeon Eom
Summary: The study reveals that neuronal nitric oxide synthase induces diastolic dysfunction by S-nitrosylation of HDAC2, suggesting a new therapeutic platform for refractory heart failure with preserved ejection fraction.
Review
Biochemistry & Molecular Biology
Amir Asgari, Paul Jurasz
Summary: Megakaryocytes are important members of the hematopoietic system, responsible for regulating vascular homeostasis through platelets. The process of megakaryopoiesis generates mature megakaryocytes which release proplatelets into blood vessels. Nitric oxide (NO) plays a modulatory role in hematopoiesis and hemostasis. This review summarizes the effect of NO and its signaling on megakaryopoiesis and thrombopoiesis under physiological and pathophysiological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Fabio Arias, Francisco Franco-Montalban, Miguel Romero, M. Dora Carrion, M. Encarnacion Camacho
Summary: The study synthesized and evaluated two isosteric series of derivatives with an imidamide scaffold targeting inducible (iNOS) and neuronal (nNOS) isoforms. The N-(3-(2-amino-5-methoxyphenyl)-3-hydroxypropyl)-4-(trifluoromethyl)benzimidamide 4i was identified as the most active iNOS inhibitor with the highest selectivity in vitro. Docking studies suggested different binding modes on both isozymes, supporting the observed selectivity towards the inducible isoform.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Arjun Pendharkar, Daniel Smerin, Lorenzo Gonzalez, Eric H. Wang, Sabrina Levy, Stephanie Wang, Shunsuke Ishizaka, Masaki Ito, Haruto Uchino, Terrance Chiang, Michelle Y. Cheng, Gary K. Steinberg
Summary: Post-stroke optogenetic stimulation and systemic nNOS inhibition both lead to functional improvements after stroke, suggesting a potentially maladaptive role of nNOS in post-stroke recovery.
TRANSLATIONAL STROKE RESEARCH
(2021)
Article
Medicine, Research & Experimental
George J. Dugbartey
Summary: Kidney transplantation is the preferred treatment for patients with kidney failure. However, ischemia-reperfusion injury (IRI) poses a significant challenge to the long-term success of this intervention. Nitric oxide (NO) has emerged as a potential candidate for mitigating IRI and preventing graft rejection in kidney transplantation. This review provides an overview of the sources and protective effects of endogenous and exogenous NO in kidney transplantation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Fabio Arias, Francisco Franco-Montalban, Miguel Romero, Juan Duarte, M. Dora Carrion, M. Encarnacion Camacho
Summary: This paper describes the design, synthesis, and biological evaluation of selective inhibitors of inducible nitric oxide synthase (iNOS). The most potent and selective compound showed inhibitory activity against iNOS without undesirable cardiovascular effects. In silico analysis predicted good drug-likeness properties for promising compounds, which also exhibited adequate cell viability. Docking studies revealed a unique binding mode for one compound and explained its selectivity towards iNOS.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Bashair M. Mussa, Amir Ali Khan, Ankita Srivastava, Sallam Hasan Abdallah
Summary: This study focused on differentiating iMSCs into PDGFR alpha-positive cells, investigating the effects of NO on cell survival, and evaluating the impact of hyperglycemia on nNOS gene expression. The results showed that differentiation was successful, and NO had a significant effect on cell survival, while hyperglycemia increased nNOS expression. This novel model can help identify new therapeutic targets for treating DGP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Angelo Bernak-Oliveira, Daniele M. Guizoni, Silvana Chiavegatto, Ana P. Davel, Luciana V. Rossoni
Summary: The study examined the role of neuronal nitric oxide synthase (nNOS) and H2O2 in endothelial vasodilation following beta-adrenergic receptor (β-AR) overstimulation, with results suggesting a protective role of nNOS in cardiovascular diseases.
Editorial Material
Plant Sciences
Francisco J. Corpas, Salvador Gonzalez-Gordo, Jose M. Palma
Summary: Nitric oxide is a crucial signaling molecule in plant physiological processes, but the enzymatic generation of nitric oxide in higher plants is still controversial.
TRENDS IN PLANT SCIENCE
(2022)
Article
Chemistry, Organic
Xiaowei Wu, Haitao Ji
JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Chemistry, Organic
Xiaowei Wu, Haitao Ji
ORGANIC & BIOMOLECULAR CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Jin Wang, Haitao Ji
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Peng Sang, Min Zhang, Yan Shi, Chunpu Li, Sami Abdulkadir, Qi Li, Haitao Ji, Jianfeng Cai
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Chemistry, Medicinal
Zhen Wang, Haitao Ji
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Qingliang Li, Rezaul M. Karim, Mo Cheng, Mousumi Das, Lihong Chen, Chen Zhang, Harshani R. Lawrence, Gary W. Daughdrill, Ernst Schonbrunn, Haitao Ji, Jiandong Chen
Review
Chemistry, Medicinal
Zhen Wang, Zilu Li, Haitao Ji
Summary: Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with cancer, and direct targeting of beta-catenin is a promising strategy but challenging. Research has identified potential small-molecule binding sites and summarized bioactive small molecules that target beta-catenin directly.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Narges K. Tafreshi, Darpan N. Pandya, Christopher J. Tichacek, Mikalai M. Budzevich, Zhen Wang, Jordan N. Reff, Robert W. Engelman, David C. Boulware, Alberto A. Chiappori, Jonathan R. Strosberg, Haitao Ji, Thaddeus J. Wadas, Ghassan El-Haddad, David L. Morse
Summary: The study demonstrates significant potential for the clinical translation of [Ac-225]Ac-DOTA-TATE for lung NENs, showing notable tumor growth delay and prolonged time to experimental endpoint.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Wen Luo, Yongqiang Zhang, Haitao Ji
Summary: The study presents a new small-molecule inhibitor that selectively disrupts the beta-catenin/BCL9 interaction, inhibits the role of the Wnt signaling pathway in cancer, and can serve as a lead compound for further optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Victor Quereda, Sylvia M. Frydman, Qianqian Ming, Vincent C. Luca, Derek R. Duckett, Haitao Ji
Summary: This study introduces a drug-like small molecule, ZW4864, which selectively disrupts the protein-protein interaction between BCL9 and beta-catenin, effectively suppressing beta-catenin signaling activation and target gene expression in a mouse model. This provides a potential therapeutic target for developing drugs targeting aberrant Wnt/beta-catenin signaling in diseases such as cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zilu Li, Min Zhang, Kevin B. Teuscher, Haitao Ji
Summary: Structure-based design and optimization led to the discovery of a small-molecule beta-catenin/BCL9 inhibitor ZL3138, which disrupts the protein-protein interaction effectively and selectively in living cells, showing potential anti-tumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Tao Xiao, Luxin Sun, Min Zhang, Zilu Li, Eric B. Haura, Ernst Schonbrunn, Haitao Ji
Summary: A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction between GRB2 and phosphotyrosine-containing proteins. Biochemical studies showed compound 7 binds with the SH2 domain of GRB2 with higher potency, while X-ray crystallographic studies revealed key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for generating cell-permeable inhibitors for the aberrant Ras-MAPK signaling cascade.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Haitao Ji
Summary: The cooperativity index, Kc, was developed to examine the binding synergy between hot spots of the ligand-protein. The spatial arrangements of hydrophilic alpha-helical hot spots in protein-protein interaction (PPI) complex structures were disclosed and quantified using novel clustering models. The driving force for the convergence of these hot spots was analyzed, allowing the development of pharmacophore models for designing new mimetics.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Harriet M. Thompson, Haitao Ji
Summary: A series of new small-molecule beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction inhibitors were reported. Among them, compound 21 showed potent inhibition in cellular context and demonstrated higher potential in regulating transcription and expression of beta-catenin target genes and suppressing survival of beta-catenin-dependent cancer cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Shelby R. Kell, Zhen Wang, Haitao Ji
Summary: Fragment-based ligand discovery (FBLD) is a successful approach for designing small-molecule protein-protein interaction (PPI) inhibitors. This article describes a computational protocol using fragment hopping for developing small-molecule PPI inhibitors and includes a case study to illustrate its efficiency. Fragment hopping enables the design of PPI inhibitors based solely on key binding features in the PPI complex structure. This approach is an open system that can incorporate different programs and software to improve its performance.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)