Article
Cell Biology
Chang-Ning Fu, Jia-Wen Song, Zhi-Peng Song, Qian-Wen Wang, Wen-Wu Bai, Tao Guo, Peng Li, Chao Liu, Shuang-Xi Wang, Bo Dong
Summary: Statin-induced skeletal injury is mediated by the excessive expression of miR-1a, leading to decreased MAP3K1 gene expression and subsequent apoptosis of skeletal muscle cells.
Review
Pharmacology & Pharmacy
Shanelle R. Shillingford, Anton M. Bennett
Summary: Phosphatases and kinases play crucial roles in maintaining the balance between dephosphorylated and phosphorylated proteins for cellular functions. Imbalance or dysfunction in their activities can lead to unfavorable cellular effects and the development of diseases. Protein tyrosine phosphatases (PTPs) are attractive therapeutic targets due to their involvement in cell signaling and diseases, but they have been challenging in drug development. This article focuses on the progress in small-molecule inhibition of the mitogen-activated protein kinase (MAPK) phosphatases (MKPs), discussing successful strategies and inhibitor discovery tools, as well as the potential future of MKP inhibition.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ling Yin, Yongji Zeng, Renya Zeng, Yuanhong Chen, Tian-Li Wang, Kerry J. Rodabaugh, Fang Yu, Amarnath Natarajan, Adam R. Karpf, Jixin Dong
Summary: PKR plays a critical role in cancer treatment by regulating sensitivity to paclitaxel through controlling Bcl2 expression, presenting as a potential therapeutic target for recurrent drug-resistant ovarian tumors.
Article
Oncology
Annamaria Massa, Caterina Peraldo-Neia, Francesca Vita, Chiara Varamo, Marco Basirico, Chiara Raggi, Paola Bernabei, Jessica Erriquez, Ivana Sarotto, Francesco Leone, Serena Marchio, Giuliana Cavalloni, Massimo Aglietta
Summary: The study demonstrates that paclitaxel has anti-tumor activity in multidrug-resistant intrahepatic cholangiocarcinoma by affecting the cell cycle and inducing apoptosis, impairing the stem cell compartment. A therapeutic regimen containing albumin-bound nanoparticle paclitaxel overcomes drug resistance and delays tumor growth, reducing glucose uptake.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biology
Guorong Li, Chanyoung Lee, A. Thomas Read, Ke Wang, Jungmin Ha, Megan Kuhn, Iris Navarro, Jenny Cui, Katherine Young, Rahul Gorijavolu, Todd Sulchek, Casey Kopczynski, Sina Farsiu, John Samples, Pratap Challa, C. Ross Ethier, W. Daniel Stamer
Summary: Netarsudil reduces glucocorticoid-induced ocular hypertension by preventing or attenuating pathologies, acting directly on conventional outflow cells. These findings warrant a randomized prospective clinical study to evaluate its superiority in lowering steroid-induced ocular hypertension.
Article
Peripheral Vascular Disease
Mohammad Shafid, Kumaravelu Jagavelu, Hina Iqbal, Pankaj Yadav, Debabrata Chanda, Neeraj Kumar Verma, Jimut Kanti Ghosh, Matthias Gaestel, Kashif Hanif
Summary: MK2 plays a significant role in pulmonary hypertension, and its inhibition may be a novel target for PH treatment. Inhibition of MK2 alleviated right ventricle pressure and hypertrophy in PH rats, improved cardiac function, reversed pulmonary vascular remodeling, and enhanced pulmonary vascular relaxation.
Article
Biochemistry & Molecular Biology
Shanelle Shillingford, Lei Zhang, Yulia Surovtseva, Sam Dorry, Elias Lolis, Anton M. Bennett
Summary: This study demonstrates the importance of a specific site (Y271) in the phosphatase domain of MKP7 for its catalytic activity and binding to p38 MAPK and JNK. Mutations in this site inhibited MKP7 function, leading to increased nuclear accumulation of p38 MAPK and JNK. These findings contribute to our understanding of the regulatory mechanisms of MKP7 and provide insights for potential therapeutic targeting of MKP7.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lijing Wang, Shuchen Gu, Fenfang Chen, Yi Yu, Jin Cao, Xinran Li, Chun Gao, Yanzhen Chen, Shuchong Yuan, Xia Liu, Jun Qin, Bin Zhao, Pinglong Xu, Tingbo Liang, Hongyan Tong, Xia Lin, Xin-Hua Feng
Summary: Loss of TGF-beta-mediated growth suppression is a major contributor to cancer development, and this study investigates the molecular mechanisms involved in the oncogene-induced modulation of TGF-beta signaling. The researchers found that the oncogenic BCR-ABL1 kinase phosphorylates and inactivates Smad4, thereby blocking the antiproliferative TGF-beta signaling. They also demonstrated that inhibition of BCR-ABL1 kinase restores the beneficial TGF-beta anti-growth responses.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Oncology
Kian-Huat Lim, Mateusz Opyrchal, Abhi Acharya, Nick Boice, Ningying Wu, Feng Gao, Jace Webster, Albert C. Lockhart, Saiama N. Waqar, Ramaswamy Govindan, Daniel Morgensztern, Joel Picus, Benjamin R. Tan, Maria Q. Baggstrom, Christopher A. Maher, Andrea Wang-Gillam
Summary: The study evaluated the efficacy and safety of the combination of AURKA inhibitor (alisertib) and paclitaxel in patients with refractory high-grade neuroendocrine tumors (NETs). The combination treatment demonstrated manageable side-effect profile and promising preliminary efficacy in high-grade NETs, warranting further testing.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Shumei Kato, Robert Porter, Ryosuke Okamura, Suzanna Lee, Ori Zelichov, Gabi Tarcic, Michael Vidne, Razelle Kurzrock
Summary: The study found that patients with tumors harboring RAS alterations with high MAPK activity had significantly longer median progression-free survival (PFS) and overall survival when treated with MEK inhibitors. This correlation between RAS-mutant cancers with greater MAPK signaling and PFS suggests potential clinical benefit of MEK inhibitor treatment.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Yen-Tze Liu, Hsin-Yu Ho, Chia-Chieh Lin, Yi-Ching Chuang, Yu-Sheng Lo, Ming-Ju Hsieh, Mu-Kuan Chen
Summary: Platyphyllenone can induce both autophagy and apoptosis in oral cancer cells by regulating multiple signaling pathways, providing a potential therapeutic option for chemoprevention against oral cancer proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Vikram Jeet Singh, Bharti Sharma, Pooja A. Chawla
Summary: The article focuses on the MAPK signaling pathway and the role of different heterocyclic compounds with nitrogen, sulfur, and oxygen in blocking the MAPK signaling pathway. Heterocyclic compounds are important due to their high potency and selectivity against various targets involved in the MAPK signaling pathway for cancer management. The potential of these compounds in inhibiting MAPK cascade and recent advancements in developing MAPK signaling pathway inhibitors are discussed in detail.
BIOORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Thomas H. Craven, Tashfeen Walton, Ahsan R. Akram, Emma Scholefield, Neil McDonald, Adam D. L. Marshall, Duncan C. Humphries, Bethany Mills, Thane A. Campbell, Annya Bruce, Joanne Mair, James W. Dear, David E. Newby, Adam T. Hill, Timothy S. Walsh, Chris Haslett, Kevin Dhaliwal
Summary: The development of a molecular imaging probe targeting neutrophil activation allowed for real-time identification of neutrophil activity in the lungs of patients, enabling biological stratification based on disease states and severity. Evaluation of the probe's imaging responses in different patient populations confirmed that the optical signal was indeed due to the probe's function and neutrophil activation.
SCIENTIFIC REPORTS
(2021)
Review
Gastroenterology & Hepatology
Benno Traub, Aileen Roth, Marko Kornmann, Uwe Knippschild, Joachim Bischof
Summary: Pancreatic cancer is a devastating disease with poor survival rates, prompting the need for new therapeutic approaches. Protein kinases play crucial roles in development and pathogenesis, making them potential targets for precision medicine in patients with deregulated kinase pathways.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aisha Alhaddad, Asmaa Radwan, Noha A. Mohamed, Eman T. Mehanna, Yasser M. Mostafa, Norhan M. El-Sayed, Shaimaa A. Fattah
Summary: This study investigated the antidepressant effect of rosiglitazone (RGZ) on dexamethasone-induced depression by regulating the function of the pAKT/p38MAPK/mTOR pathway and NGF through AMPK. The results revealed that RGZ significantly inhibited the activity of the pAKT/p38MAPK/mTOR/4EBP1 pathway and activated NGF in brain cells, suggesting its potential as a new antidepressant for the treatment of MDD.
Article
Oncology
Zhenyu Yang, Dan Wang, James K. Johnson, Laura E. Pascal, Keita Takubo, Raghunandan Avula, Anish Bhaswanth Chakka, Jianhua Zhou, Wei Chen, Mingming Zhong, Qiong Song, Hui Ding, Zeyu Wu, Uma R. Chandran, Taber S. Maskrey, Joel B. Nelson, Peter Wipf, Zhou Wang
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Chemistry, Medicinal
Donna M. Huryn, David J. P. Kornfilt, Peter Wipf
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Pediatrics
Chhinder P. Sodhi, Peter Wipf, Yukihiro Yamaguchi, William B. Fulton, Mark Kovler, Diego F. Nino, Qinjie Zhou, Emilyn Banfield, Adam D. Werts, Mitchell R. Ladd, Rachael H. Buck, Karen C. Goehring, Thomas Prindle, Sanxia Wang, Hongpeng Jia, Peng Lu, David J. Hackam
Summary: The study showed that human milk oligosaccharides 2'-FL and 6'-SL can prevent NEC through inhibition of TLR4 signaling, while lactose cannot. The results indicate that these HMOs reduced NEC occurrence in mouse and piglet models.
PEDIATRIC RESEARCH
(2021)
Article
Endocrinology & Metabolism
Nicolas Manzke Glanzel, Mateus Grings, Nevton Teixeira da Rosa-Junior, Leila Maria Cereta de Carvalho, Al-Walid Mohsen, Peter Wipf, Moacir Wajner, Jerry Vockley, Guilhian Leipnitz
Summary: Sulfite oxidase (SO) deficiency causes tissue sulfite accumulation and patients present with seizures and neurological damage. Treatment is mainly supportive. Study shows that treatment with JP4-039 can prevent or attenuate oxidative stress and apoptosis induced by sulfite injection.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Pediatrics
Chhinder P. Sodhi, Peter Wipf, Yukihiro Yamaguchi, William B. Fulton, Mark Kovler, Diego F. Nino, Qinjie Zhou, Emilyn Banfield, Adam D. Werts, Mitchell R. Ladd, Rachael H. Buck, Karen C. Goehring, Thomas Prindle, Sanxia Wang, Hongpeng Jia, Peng Lu, David J. Hackam
PEDIATRIC RESEARCH
(2021)
Review
Chemistry, Organic
Thanh T. Nguyen, Peter Wipf
Summary: The development of intramolecular Diels-Alder cycloaddition of azole heterocycles has significantly impacted the efficient preparation of heterocyclic intermediates and natural products. While IMDAO reactions have been utilized as a key step in several synthetic schemes, IMDAI and IMDAT cycloadditions have been less studied. The review also highlights some drawbacks, such as the challenging preparation of IMDA precursors, and provides perspectives on expanding the transformations for target-directed syntheses.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Organic
Ettore J. Rastelli, Doris Yue, Caroline Millard, Peter Wipf
Summary: The polypropylene continuous-photoflow cell developed through 3D printing is cost-effective and suitable for photo-oxygenation reactions using ambient air as the sole co-reactant. It offers the benefits of scalability and a short residence time under blue LED light, which minimizes the formation of dark, insoluble decomposition products.
Article
Biochemistry & Molecular Biology
Yasaman Hamedani, Rayane Brinck Teixeira, Catherine Karbasiafshar, Peter Wipf, Sankha Bhowmick, M. Ruhul Abid
Summary: The study demonstrates that electrospinning methods can be utilized to load mitochondria-targeted antioxidants onto biocompatible nanofibrous scaffolds, preserving their antioxidant properties upon release and improving cell function.
Article
Oncology
Li Wan, Jun Yin, John Skoko, Russell Schwartz, Mei Zhang, Philip R. LeDuc, Carola A. Neumann
Summary: Disease models, including in vitro cell culture and animal models, have significantly contributed to the development of diagnostics and treatments in the past few decades. Traditional drug screening methods have been limited by a lack of adequate mimicry of critical in vivo features. The development of a new 3D dynamic drug delivery system for cancer drug screening provides reliable data and represents a direction for future drug sensitivity predicting algorithms.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
John S. Lazo, Elizabeth R. Sharlow, Robert Cornelison, Duncan J. Hart, Danielle C. Llaneza, Anna J. Mendelson, Ettore J. Rastelli, Nikhil R. Tasker, Charles N. Landen, Peter Wipf
Summary: High grade serous ovarian cancer often becomes drug resistant and recurrent. A study showed that high expression of Protein Tyrosine Phosphatase of Regenerating Liver-3 (PRL3) is associated with poor patient survival in both early and late stages of ovarian cancer. A potent allosteric small molecule PTP4A3 inhibitor, JMS-053, was found to reduce high grade serous ovarian cancer cell survival. Results also showed that controlling PTP4A3 can affect cell migration and the inhibitor JMS-053 can lead to reduced cell migration.
Article
Biochemistry & Molecular Biology
Keishla M. Rodriguez-Graciani, Xavier R. Chapa-Dubocq, Esteban J. Ayala-Arroyo, Ivana Chaves-Negron, Sehwan Jang, Nataliya Chorna, Taber S. Maskrey, Peter Wipf, Sabzali Javadov
Summary: In this study, the metabolome of H9c2 cardioblasts during RSL3-induced ferroptosis was elucidated using gas chromatography-mass spectrometry. The results showed that RSL3 decreased the levels of amino acids involved in glutathione synthesis and increased the levels of saturated fatty acids. RSL3 also significantly altered the levels of mitochondrial tricarboxylic acid cycle intermediates. Furthermore, ferrostatin-1, XJB-5-131, and TSM-1005-44 protected against RSL3-induced cell death and preserved the metabolomic profile of the cells.
Article
Biochemistry & Molecular Biology
Merlin Airik, Haley Arbore, Elizabeth Childs, Amy B. Huynh, Yu Leng Phua, Chi Wei Chen, Katherine Aird, Sivakama Bharathi, Bob Zhang, Peter Conlon, Stanislav Kmoch, Kendrah Kidd, Anthony J. Bleyer, Jerry Vockley, Eric Goetzman, Peter Wipf, Rannar Airik
Summary: Karyomegalic interstitial nephritis (KIN) is a genetic kidney disease caused by recessive mutations in the FAN1 DNA repair enzyme. The disease is characterized by genomic instability and mitotic abnormalities in tubular epithelial cells. Hypersensitivity to endogenous reactive oxygen species (ROS) is identified as a key factor in the pathogenesis of KIN, leading to chronic oxidative and double-strand DNA damage.
Correction
Pharmacology & Pharmacy
M. P. Czub, A. M. Boulton, E. J. Rastelli, N. R. Tasker, T. S. Maskrey, I. K. Blanco, K. E. McQueeney, J. H. Bushweller, W. Minor, P. Wipf, E. R. Sharlow, J. S. Lazo
MOLECULAR PHARMACOLOGY
(2020)
Meeting Abstract
Oncology
M. Epperly, J. Yu, J. P. van Pijkeren, B. Methe, K. Li, R. Fisher, J. Lundy, X. Zhang, D. Shields, W. Hou, B. Leibowitz, P. Wipf, L. Alexander, M. S. Huq, H. Wang, J. S. Greenberger
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2020)
Meeting Abstract
Oncology
J. Lazo, N. Tasker, E. Rastelli, P. Wipf, E. Sharlow
EUROPEAN JOURNAL OF CANCER
(2020)