Review
Medicine, General & Internal
Luca Pagano, Jason William Lee, Matteo Posarelli, Giuseppe Giannaccare, Stephen Kaye, Alfredo Borgia
Summary: Rho kinase inhibitors, such as ripasudil and netarsudil, have emerged as promising treatment options in ophthalmology, particularly for glaucoma and corneal pathology. They have been shown to be effective in both in vitro and clinical studies. Their applications also extend to surgical procedures where they aid in visual recovery, scar reduction, and intraocular pressure control.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Taslim A. Al-Hilal, Mohammad Anwar Hossain, Ahmed Alobaida, Farzana Alam, Ali Keshavarz, Eva Nozik-Grayck, Kurt R. Stenmark, Nadezhda A. German, Fakhrul Ahsan
Summary: The study developed a hypoxia-activated prodrug of fasudil that selectively suppresses ROCK activity under hypoxic conditions, exhibiting antiproliferative effects on disease-afflicted pulmonary arterial smooth muscle cells and pulmonary arterial endothelial cells. The prodrug has a long plasma half-life and does not affect systemic blood pressure.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Lu Liu, Xuejiao Yang, Jingjing Zhang, Wenlan Jiang, Tianyu Hou, Yao Zong, Haiqing Bai, Kun Yang, Xian Yang
Summary: In this study, it was found that long non-coding RNA small nucleolar RNA host gene 11 (SNHG11) regulates the Wnt/β-catenin signaling pathway in trabecular meshwork (TM) cells through the Rho/ROCK pathway and β-catenin phosphorylation, affecting cell proliferation, migration, apoptosis, and autophagy. These findings suggest that SNHG11 plays a crucial role in the pathogenesis of glaucoma and could be a potential therapeutic target.
Review
Genetics & Heredity
Guangzhao Guan, Richard D. D. Cannon, Dawn E. E. Coates, Li Mei
Summary: The mechanical properties of cells play an important role in tissue homeostasis and various cellular processes. These properties are determined by the cytoskeleton, which is a complex and dynamic network of microfilaments, intermediate filaments, and microtubules. The Rho-kinase/ROCK signaling pathway regulates the architecture of this cytoskeletal network, influencing cell behavior.
Article
Multidisciplinary Sciences
Mengwei Li, Limei Zhang, Xinyan Liu, Guoqiang Wang, Jian Lu, Jifeng Guo, Hongjie Wang, Jinpeng Xu, Yi Zhang, Na Li, You Zhou
Summary: This study found that low-intensity exercise training can improve the heart function and structure of spontaneously hypertensive rats by inhibiting the RhoA/ROCK signaling pathway, providing further evidence for this protective effect.
SCIENTIFIC REPORTS
(2022)
Article
Ophthalmology
Manoj Mathur, P. Ratnam, S. J. Saikumar, Manuel John, Siddharth Ravishankar, M. B. Dinesh, Priya Chandil, Kishore Pahuja, Vidya Cherlikar, Sunny Wadhwani, Pankaj Bendale, Ajit Hazari, Rajesh Mishra, Susheel Deshmukh, Rahul Achlerkar, Devang Shah, Chanda Hingorani, Kaivan Shah, Pratik Topiwala, Sheetal Jani, Viral Rana, Nilay Majumdar, Debasis Chakrabarti, Rituparna Dey, Debabrata Halder, Sumit Choudhury, Ajeet Kumar, Sasmita Das, Ashok Nanda, Vidya Kumar, Rama Dubey, Gulam Kamdar, Alka Pandey, Sheetal Kishanpuria, Rajat Srivastava, Parul Singh, Sunil Verma, Neha Sharma, Rajeev Gupta
Summary: This study demonstrates that monotherapy with netarsudil 0.02% w/v solution is safe and effective as a first-line treatment for primary open-angle glaucoma and ocular hypertension. Patients only experienced a small number of tolerable adverse effects.
INDIAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Veterinary Sciences
Vanessa Y. Yang, Paul E. Miller, Deborah A. Keys, Noelle C. La Croix
Summary: The study found that once-daily dosing of netarsudil did not significantly reduce intraocular pressure in normotensive dogs, while twice-daily dosing resulted in a statistically significant but clinically insignificant reduction. Adverse events were limited to transient mild-to-moderate conjunctival hyperemia.
VETERINARY OPHTHALMOLOGY
(2021)
Article
Chemistry, Medicinal
Upul K. Bandarage, John Court, Huai Gao, Suganthini Nanthakumar, Jon H. Come, Simon Giroux, Jeremy Green
Summary: The study extended the structure-activity relationship exploration of the 7-azaindole series to identify new compounds with excellent ROCK potency, PKA selectivity, and stability in microsomes and hepatocytes for further evaluation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Emran Hossen, Yasuhiro Funahashi, Md. Omar Faruk, Rijwan Uddin Ahammad, Mutsuki Amano, Kiyofumi Yamada, Kozo Kaibuchi
Summary: Rho-kinase phosphorylates PSD-93 downstream of NMDARs, increasing its association with PSD-95 and NMDARs to regulate structural synaptic plasticity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Marie Suzuki, Yohei Suzuki, Ryohei Komori, Yusuke Orii, Shogo Arimura, Kentaro Iwasaki, Yoshihiro Takamura, Masaru Inatani
Summary: This study investigated the effect of topical administration of ripasudil ophthalmic solution on aqueous outflow in the episcleral vein of the human eye. The results showed that the ripasudil group had significantly greater dilation of the aqueous column width than the latanoprost group at 2 and 8 hours after instillation.
SCIENTIFIC REPORTS
(2022)
Review
Behavioral Sciences
RuoLan Cai, YangYang Wang, ZhenTing Huang, Qian Zou, YinShuang Pu, Changyin Yu, Zhiyou Cai
Summary: ROCK activation can promote the occurrence of Alzheimer's disease and may involve a positive feedback loop between Aβ and ROCK. Additionally, ROCK can also promote the formation of neurofibrillary tangles and exacerbate neuroinflammatory responses.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Tetsu Kimura, Yuta Horikoshi, Chika Kuriyagawa, Yukitoshi Niiyama
Summary: Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Luqing Song, Tao Wu, Li Zhang, Jin Wan, Zheng Ruan
Summary: The phenolic acid CGA can protect the intestinal barrier by inhibiting ROCK/MLCK signaling pathways and relieving ER stress. Three other substances were also found to stabilize intestinal homeostasis.
Article
Pharmacology & Pharmacy
Tong Liu, Ning Zhang, Lingya Kong, Sijie Chu, Ting Zhang, Guangdi Yan, Donglai Ma, Jun Dai, Zhihong Ma
Summary: Paeoniflorin can alleviate liver injury in hypercholesterolemic rats through its antioxidant and anti-inflammatory effects, as well as the ROCK/AMPK/SREBP-1c signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Environmental Sciences
Junyan Yan, Yaxin Tang, Xin Zhong, Huarong Huang, Haonan Wei, Yulei Jin, Yanjiang He, Jinqiao Cao, Lifang Jin, Baowei Hu
Summary: Exposure to carbon blacks (CBs) can activate the RhoA/ROCK pathway in mice lungs, leading to the progression of pulmonary fibrosis. However, treatment with ROCK inhibitor Y-27632 can attenuate this activation and inhibit the development of pulmonary fibrosis.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Neurosciences
Jingyi Wang, Angelo Blasio, Holly L. Chapman, Christelle Doebelin, Victor Liaw, Alexander Kuryatov, Simone M. Giovanetti, Jon Lindstrom, Li Lin, Michael D. Cameron, Theodore M. Kamenecka, Matthew B. Pomrenze, Robert O. Messing
NEUROPSYCHOPHARMACOLOGY
(2020)
Article
Neurosciences
Travis W. Grim, Cullen L. Schmid, Edward L. Stahl, Fani Pantouli, Jo-Hao Ho, Agnes Acevedo-Canabal, Nicole M. Kennedy, Michael D. Cameron, Thomas D. Bannister, Laura M. Bohn
NEUROPSYCHOPHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Gregory H. Bird, Accalia Fu, Silvia Escudero, Marina Godes, Kwadwo Opoku-Nsiah, Thomas E. Wales, Michael D. Cameron, John R. Engen, Nika N. Danial, Loren D. Walensky
ACS CHEMICAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Zhi-Chen Wu, Michael D. Cameron, Dale L. Boger
ACS INFECTIOUS DISEASES
(2020)
Article
Chemistry, Multidisciplinary
Hafeez S. Haniff, Laurent Knerr, Xiaohui Liu, Gogce Crynen, Jonas Bostrom, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Michael D. Cameron, Ilyas Yildirim, Malin Lemurell, Matthew D. Disney
Article
Chemistry, Medicinal
Hua Lin, Kfir Sharabi, Li Lin, Claudia Ruiz, Di Zhu, Michael D. Cameron, Scott J. Novick, Patrick R. Griffin, Pere Puigserver, Theodore M. Kamenecka
Summary: Despite the availability of numerous pharmacotherapies for type 2 diabetes (T2D), challenges remain in achieving glycemic control. Novel glucose-lowering strategies are currently under clinical investigation, indicating the need for more effective treatments. A compound known as SR18292 has shown potential in reducing glucose release and improving hyperglycemia in diabetic mouse models, suggesting a new therapeutic approach for T2D.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Nelson E. Bruno, Jerome C. Nwachukwu, Sathish Srinivasan, Charles C. Nettles, Tina Izard, Zhuang Jin, Jason Nowak, Michael D. Cameron, Siddaraju V. Boregowda, Donald G. Phinney, Olivier Elemento, Xu Liu, Eric A. Ortlund, Rene Houtman, Diana A. Stavreva, Gordon L. Hager, Theodore M. Kamenecka, Douglas J. Kojetin, Kendall W. Nettles
Summary: The study found that ligand class analysis can predict the effects of glucocorticoid receptor ligands on myocyte metabolism and protein balance, identifying compounds with muscle-sparing and protein synthesis effects. This method provides a new approach to understand the link between the ligand-receptor interface and physiological outcomes.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Neurosciences
Fani Pantouli, Travis W. Grim, Cullen L. Schmid, Agnes Acevedo-Canabal, Nicole M. Kennedy, Michael D. Cameron, Thomas D. Bannister, Laura M. Bohn
Summary: The mu opioid receptor-selective agonist, SR-17018, demonstrates signaling bias by preferentially activating GTP gamma S binding over beta arrestin2 recruitment in cellular assays. It shows potent and efficacious antinociceptive effects in various pain models, with particular efficacy in chemotherapeutic-induced neuropathic pain, and retains its effectiveness upon repeated dosing.
Article
Biochemistry & Molecular Biology
Saif N. Haify, Ronald A. M. Buijsen, Lucas Verwegen, Lies-Anne W. F. M. Severijnen, Helen de Boer, Valerie Boumeester, Roos Monshouwer, Wang-Yong Yang, Michael D. Cameron, Rob Willemsen, Matthew D. Disney, Renate K. Hukema
Summary: FXTAS is a neurodegenerative disorder caused by CGG-repeat expansion in the FMR1 gene, with potential targeted therapy through small molecule 1a blocking the translation of toxic FMRpolyG protein. Research demonstrates efficacy of small molecule therapy in reducing FMRpolyG-positive inclusions and insoluble protein levels in an FXTAS mouse model, suggesting promise for treating CGG(exp)-mediated diseases.
HUMAN MOLECULAR GENETICS
(2021)
Article
Oncology
Jieun Son, Jaebong Jang, Tyler S. Beyett, Yoonji Eum, Heidi M. Haikala, Alyssa Verano, Mika Lin, John M. Hatcher, Nicholas P. Kwiatkowski, Pinar O. Eser, Michael J. Poitras, Stephen Wang, Man Xu, Prafulla C. Gokhale, Michael D. Cameron, Michael J. Eck, Nathanael S. Gray, Pasi A. Janne
Summary: This study describes a new mutant-selective HER2 kinase inhibitor, JBJ-08-178-01, that reduces both kinase activity and protein levels of HER2 in lung cancer. The compound exhibits strong antitumoral activity and selective inhibition towards HER2 mutants over wild-type EGFR.
Article
Biochemistry & Molecular Biology
Huiyong Ma, Tarsis Brust, Kevin J. Frankowski, Kimberly M. Lovell, Michael D. Cameron, Laura M. Bohn, Jeffrey Aube
Summary: This study focused on the modification of a sulfonamide-based KOR antagonist series, resulting in a 4-fold increase in potency compared to the lead compound. The improved analogue exhibited suitable brain levels and a shorter clearance time.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Rita Fuerst, Jun Yong Choi, Anna M. Knapinska, Michael D. Cameron, Claudia Ruiz, Amber Delmas, Mark S. Sundrud, Gregg B. Fields, William R. Roush
Summary: This study focused on optimizing interactions near the Zn2+ binding site of MMP-13 enzyme by using a known MMP-13 inhibitor as a starting point. A new compound, 32, containing an oxetane ring, was found to have complete inhibition of collagenolysis in vitro and excellent selectivity among the MMP family. Docking studies suggested that the oxetane ring in compound 32 was oriented towards the Zn2+ ion, chelating the metal ion. In vivo pharmacokinetic studies demonstrated a promising concentration of compound 32 within the synovial fluid of the rat knee joint, making it a potential lead compound for further development in osteoarthritis.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Samantha M. Meyer, Toru Tanaka, Patrick R. A. Zanon, Jared T. Baisden, Daniel Abegg, Xueyi Yang, Yoshihiro Akahori, Zainab Alshakarchi, Michael D. Cameron, Alexander Adibekian, Matthew D. Disney
Summary: This study utilized a DNA-encoded library to identify a compound that activates ribonuclease activity and incorporated it into the design of a next-generation ribonuclease targeting chimera. The developed chimera successfully alleviated the cellular phenotype of triple-negative breast cancer cells. This work demonstrates the potential of DNA-encoded libraries in identifying compounds with effector functions in heterobifunctional compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Santanu Mondal, Yongzhi Chen, Gordon J. Lockbaum, Sudeshna Sen, Sauradip Chaudhuri, Archie C. Reyes, Jeong Min Lee, Arshia N. Kaur, Nadia Sultana, Michael D. Cameron, Scott A. Shaffer, Celia A. Schiffer, Katherine A. Fitzgerald, Paul R. Thompson
Summary: The newly discovered M-Pro inhibitors SM141 and SM142 show promising potential as antiviral drugs against SARS-CoV2, effectively blocking viral replication. These inhibitors work by dual inhibition of M-Pro and CatL, reducing viral replication and improving survival rates in infected mice.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Parasitology
Katalin Toth, Sevan Alwan, Susan Khan, Stanton F. McHardy, Philip T. LoVerde, Michael D. Cameron
Summary: The antischistosomal drug OXA requires activation by a sulfotransferase within the parasitic worm for killing. However, its clinical plasma concentrations are much lower than the in vitro efficacious concentration for schistosomal killing. By modeling the pharmacokinetic data, it was determined that the parasite resides in the vasculature between the intestine and the liver, which explains the required human dose. In silico models and follow-up PK studies in mice confirmed the dose needed to recapitulate human conditions.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2023)
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)
