Article
Pharmacology & Pharmacy
Yuan -Yuan Hei, Si Wang, Xiao-Xiao Xi, Hai-Peng Wang, Yuanxu Guo, Minhang Xin, Congshan Jiang, Shemin Lu, San-Qi Zhang
Summary: In this study, a series of fluoroquinolone derivatives were synthesized and compound A36 was found to be a potent and specific inhibitor of miRNA-21. A36 significantly reduced the expression of miRNA-21 and increased the expression of its target genes in HeLa cells. A36 exhibited antiproliferative activity against multiple tumor cell lines without cytotoxicity in normal cells. Furthermore, A36 induced apoptosis, arrested cells at the G(0)/G(1) phase, and inhibited cell-colony formation in HeLa cells. This study demonstrated that A36 is a novel miRNA-21 inhibitor.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Brandoch Cook, Nicholas Walker, Qisheng Zhang, Shuibing Chen, Todd Evans
Summary: Bone fractures are commonly resolved through natural processes of osteogenic regeneration and bone remodeling, but issues with bone healing often arise in aging-related disorders like Alzheimer's disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Takeshi Tanaka, Takaharu Asano, Takehito Okui, Shiori Kuraoka, Sasha A. Singh, Masanori Aikawa, Elena Aikawa
Summary: Vascular calcification is a cardiovascular disorder with no therapeutic options. A recent study discovered that the existing drug niclosamide can inhibit vascular calcification by suppressing the CROT pathway, indicating its potential as a non-invasive treatment option for this condition.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Samer Hanna, Riham Aly, Ghada Nour Eldeen, Alberto Adanero Velasco, Ruth Perez Alfayate
Summary: This study investigated the potential role of CHIR99021 and tideglusib as GSK-3 inhibitors in regenerative dentistry. The results showed that both small molecules were safe and effective in promoting the proliferation and maintaining the stemness of human dental pulp stem cells (hDPSCs).
Review
Pharmacology & Pharmacy
Ke Wu, Eduard Karapetyan, John Schloss, Jaydutt Vadgama, Yong Wu
Summary: In this article, the recent advancements in small molecule drug design are outlined with a focus on structural perspective. Protein structure prediction methods are compared and the role of ligand binding pocket in structure-based drug design is explored. Various structural features such as functional groups, stereochemistry, and molecular weight are examined for optimizing drug candidates. Computational tools like molecular docking and virtual screening are discussed for predicting and refining drug candidate structures. Examples of drug candidates designed based on their molecular structure are presented and future directions in the field are discussed. Integrating structural information with other valuable data sources can improve the drug discovery process, leading to the identification of novel therapeutics with improved efficacy, specificity, and safety profiles.
DRUG DISCOVERY TODAY
(2023)
Review
Biochemistry & Molecular Biology
Hyeon Jin Kim, Mi Suk Jeong, Se Bok Jang
Summary: The influenza virus causes significant human morbidity and mortality worldwide. Developing new anti-influenza drugs is urgently needed, with small molecules targeting NS1 being identified as a potential pathway for drug development. NS1 plays a crucial role in host antiviral responses, making it a key target for new therapeutic interventions against the virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Daniel C. Schultz, Li Pan, Tiffany Wang, Conner Booker, Iram Hyder, Laura Hanold, Garret Rubin, Yousong Ding, Jiayuh Lin, Chenglong Li
Summary: In the past 25 years, efforts have been made to develop small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved. This study used a structure-based drug design approach and carbohydrate building blocks to synthesize novel IL-6 signaling inhibitors targeting glycoprotein 130 (gp130). LS-TG-2P and LS-TF-3P were identified as promising lead compounds with preferential activity against the IL-6 signaling pathway. These compounds show potential for further development as IL-6 signaling inhibitors.
Review
Biochemistry & Molecular Biology
Christopher W. Schultz, Avinoam Nevler
Summary: This article provides an in-depth analysis of the history of Pyrvinium as a therapeutic, the rationale and data supporting its use as an anticancer agent, and the challenges associated with repurposing Pyrvinium as an anti-cancer agent. Despite the evidence supporting Pyrvinium's efficacy against cancer through various mechanisms, it has not yet been repurposed for cancer treatment and may face challenges.
Article
Chemistry, Medicinal
Lewis D. Pennington, Ingo Muegge
Summary: Modern small molecule drug discovery requires holistic drug design for multiparameter optimization, strategically using multiple drug design approaches based on the goal and stage of the drug discovery program, the quantity and quality of data for analyses, and the availability and accuracy of predictive models to increase the efficiency and success rate of small molecule drug discovery.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Pharmacology & Pharmacy
Jaka Dernovsek, Tihomir Tomasic
Summary: The Hsp90 family, including TRAP-1, Grp94, Hsp90 alpha, and Hsp9013, has been extensively studied as a potential target for cancer, neurological disorders, and infectious diseases. Non-selective Hsp90 inhibitors have not been successful due to lack of efficacy and induction of heat shock response. Developing selective inhibitors for specific Hsp90 isoforms has become a new approach.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Yunfeng Sun, Lulu Zheng, Bo Yang, Shuyu Ge, Qiang Li, Mingwan Zhang, Shenghui Shen, Yin Ying
Summary: This study investigated the potential of a series of novel non-naphthalene derivatives as Keap1-Nrf2 protein-protein interaction inhibitors for myocarditis treatment. The optimized compound K22 showed the highest metabolic stability and demonstrated inhibitory activities against Keap1-Nrf2 interaction in cell experiments. Moreover, K22 effectively activated Nrf2 and increased the expression of Nrf2-regulated genes in H9c2 cells. Pre-treatment with K22 also mitigated LPS-induced cell damage by reducing inflammatory factors and reactive oxygen species levels, without mutagenic effects in the Ames test.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jiahui Fu, Yushang Yang, Lingjuan Zhu, Yi Chen, Bo Liu
Summary: This perspective article summarizes the different roles of protein kinases in autophagy and discusses the potential use of small-molecule compounds for targeted therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sama Shamloo, Andreas Kloetgen, Stavroula Petroulia, Kathryn Hockemeyer, Sonja Sievers, Aristotelis Tsirigos, Ioannis Aifantis, Jochen Imig
Summary: The incidence of melanoma, a commonly occurring cancer, has been increasing. Advanced-stage melanoma patients have poor prognoses compared to earlier stages. Targeted therapies for advanced-stage melanomas have been effective, but patients develop BRAF-inhibitor resistance. This resistance is mainly driven by mutations in the MAPK pathway, but other factors such as lncRNAs are still poorly understood. A comprehensive study on lncRNA expression and screening for BRAF inhibitor resistance can provide valuable insights for potential combinatorial treatment approaches.
Article
Multidisciplinary Sciences
Marua Abu Risha, Asghar Ali, Puntita Siengdee, Nares Trakooljul, Fiete Haack, Dirk Dannenberger, Klaus Wimmers, Siriluck Ponsuksili
Summary: Temperature stress can alter the expression of genes involved in Wnt signaling pathways in C2C12 myoblasts cells, with severe heat stress significantly affecting the transcripts of various key genes. Under heat stress, inhibitors of Wnt/β-catenin pathway and negative regulators are activated, while under cold stress, cell membrane receptors and members of Wnt/Ca+2 signaling pathway are downregulated. These findings suggest a correlation between Wnt signaling and energy metabolism under thermal stress.
Review
Health Care Sciences & Services
Maria Dolores Moya-Garzon, Jose Antonio Gomez-Vidal, Alfonso Alejo-Armijo, Joaquin Altarejos, Juan Roberto Rodriguez-Madoz, Miguel Xavier Fernandes, Eduardo Salido, Sofia Salido, Monica Diaz-Gavilan
Summary: Primary hyperoxalurias (PHs) are a group of inherited disorders affecting hepatic glyoxylate metabolism, leading to harmful calcium oxalate crystal accumulation. Developments in small molecule enzyme inhibitors targeting key enzymes show promise for more effective and safe therapeutic options in treating PHs.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Takuya Osada, Erika J. Crosby, Kensuke Kaneko, Joshua C. Snyder, Joshua D. Ginzel, Chaitanya R. Acharya, Xiao-Yi Yang, Thomas J. Polascik, Ivan Spasojevic, Rendon C. Nelson, Amy Hobeika, Zachary C. Hartman, Leonard M. Neckers, Andre Rogatko, Philip F. Hughes, Jiaoti Huang, Michael A. Morse, Timothy Haystead, H. Kim Lyerly
Summary: A noninvasive test utilizing the activity of Hsp90 has been developed to differentiate aggressive prostate cancer from less harmful types. In a human study, systemically administered HS196 was able to detect malignant nodules and showed greater uptake in secretory cells.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Shinya Abe, Hiroshi Nagata, Erika J. Crosby, Yoshiyuki Inoue, Kensuke Kaneko, Cong-Xiao Liu, Xiao Yang, Tao Wang, Chaitanya R. Acharya, Pankaj Agarwal, Joshua Snyder, William Gwin, Michael A. Morse, Pei Zhong, Herbert Kim Lyerly, Takuya Osada
Summary: By physically disrupting the tumor microenvironment (TME) through mechanical high-intensity focused ultrasound (M-HIFU), the activation status of tumor-associated macrophages (TAMs) can be changed, leading to enhanced T-cell infiltration. When combined with anti-PD-L1 antibody, M-HIFU can mediate superior systemic antitumor immune responses and suppress distant tumor growth.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Li-Chung Tsao, Erika J. Crosby, Timothy N. Trotter, Junping Wei, Tao Wang, Xiao Yang, Amanda N. Summers, Gangjun Lei, Christopher A. Rabiola, Lewis A. Chodosh, William J. Muller, Herbert Kim Lyerly, Zachary C. Hartman
Summary: This study reveals that the combination therapy of trastuzumab and pertuzumab activates the classical complement pathway to exert therapeutic effects. The expression of tumor C1q is positively associated with survival outcome in HER2(+) breast cancer patients, while complement regulators CD55 and CD59 are inversely correlated with outcome. Thus, complement activity plays a significant role in clinical therapeutic efficacy.
Review
Biotechnology & Applied Microbiology
Michael A. Morse, Erika J. Crosby, Jeremy Force, Takuya Osada, Amy C. Hobeika, Zachary C. Hartman, Peter Berglund, Jonathan Smith, H. Kim Lyerly
Summary: Therapeutic cancer vaccines use different platforms, such as messenger RNAs (mRNA), for antigen delivery. Self-replicating RNAs (srRNA) increase epitope expression and have been derived from positive-strand RNA viruses. Clinical stage srRNA vectors have shown positive results in encoding tumor antigens and adverse events have been minimal. Recent development of fully synthetic srRNA technologies shows promise for future vaccines.
CANCER GENE THERAPY
(2023)
Editorial Material
Biotechnology & Applied Microbiology
Herbert Kim Lyerly
CANCER GENE THERAPY
(2023)
Editorial Material
Oncology
Erika J. Crosby, Zachary C. Hartman, H. Kim Lyerly
Summary: A vaccine targeted at HER2 can prime T cells for ex vivo expansion and adoptive transfer with minimal toxicity. This treatment modality can lead to intramolecular epitope spreading in most patients and potentially improve outcomes for patients with metastatic HER2-positive breast cancer.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Takuya Osada, Xiaoning Jiang, Yuhang Zhao, Mengyue Chen, Benjamin C. Kreager, Huaiyu Wu, Howuk Kim, Jun Ren, Joshua Snyder, Pei Zhong, Michael A. Morse, H. Kim Lyerly
Summary: Mechanical high-intensity focused ultrasound (M-HIFU), including histotripsy, is a non-invasive and non-thermal ablation technology that has shown initial safety and efficacy in treating malignant liver tumors. In addition to tissue ablation, M-HIFU has the potential to stimulate local and systemic antitumor immune response in preclinical models and clinical trials.
INTERNATIONAL JOURNAL OF HYPERTHERMIA
(2023)
Article
Medicine, Research & Experimental
Timothy N. Trotter, Carina E. Dagotto, Delila Serra, Tao Wang, Xiao Yang, Chaitanya R. Acharya, Junping Wei, Gangjun Lei, H. Kim Lyerly, Zachary C. Hartman
Summary: This study reveals that dormant tumor cells can evade immune detection by utilizing tolerance mechanisms to alter the T cell microenvironment. The researchers found that dormant tumor cells can initiate immune responses but also promote the accumulation of regulatory T cells, inhibiting the activity of CD8+ killer T cells. Additionally, a protein called DKK3 derived from the tumor cells is critical for this suppression of the immune system and is associated with poor survival and immunosuppression in human breast cancers. Targeting these mechanisms, such as DKK3, may render dormant tumors susceptible to immunotherapies.
Meeting Abstract
Oncology
Zelanna Goldberg, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou, Jessica Sparks, Darina Spasova, Shigeki Miyake-Stoner, Christopher A. Rabiola, Erika J. Crosby, Zachary C. Hartman, Herbert K. Lyerly, Nathaniel Wang, Parinaz Aliahmad
Meeting Abstract
Oncology
Zelanna Goldberg, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou, Jessica Sparks, Darina Spasova, Shigeki Miyake-Stoner, Zachary C. Hartman, Christopher A. Rabiola, Erika J. Crosby, Herbert K. Lyerly, Nathaniel Wang, Parinaz Aliahmad
Meeting Abstract
Oncology
Bin-Jin Hwang, Erika Crosby, Timothy Trotter, Li-Chung Tsao, Tao Wang, Xiao Yang, Herbert Kim Lyerly, Zachary Hartman
Meeting Abstract
Oncology
Timothy N. Trotter, Delila Serra, Carina Dagotto, Tao Wang, Xiao Yang, Junping Wei, Gangjun Lei, H. Kim Lyerly, Zachary C. Hartman
Review
Biotechnology & Applied Microbiology
Anchit Bhagat, Herbert K. Lyerly, Michael A. Morse, Zachary C. Hartman
Summary: This review summarizes the progress in the development of CEA vaccines, demonstrating their ability to elicit immune response and improve clinical outcomes, but further confirmation is needed.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)
Proceedings Paper
Acoustics
Mengyue Chen, Howuk Kim, Bohua Zhang, Waston Yang, Takuya Osada, Erika J. Crosby, H. Kim Lyerly, Xiaoning Jiang
Summary: Ultrasound has shown promise in cancer immunotherapy, but current transducers have limitations. This study developed a miniaturized ultrasound transducer for intracorporeal drug/gene delivery through sonoporation, which could be potentially used in intratumoral immunotherapy.
2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)
(2022)
Article
Oncology
Darya Kizub, Cathyryne K. Manner, Katy Graef, Bello Abubakar, Jackson Orem, Folakemi Odedina, Mojisola Christianah Adeyeye, Gertrude Nakigudde, Kassa Ayalew, Chitkala Kalidas, Herbert Kim Lyerly, Thea Norman, Lola Fashoyin-Aje, Jamie Freedman, Jennifer Dent, Bill Cance, Julie Gralow
Summary: Patients of African ancestry are underrepresented in cancer clinical trials, despite experiencing high mortality rates. A satellite session was held to discuss the perspectives and priorities of stakeholders in bringing early-stage cancer trials to Africa, resulting in agreed-upon action steps.
JCO GLOBAL ONCOLOGY
(2022)