Review
Pharmacology & Pharmacy
Vigneshwaran Namasivayam, Senthikumar Palaniappan, Murugesan Vanangamudi
Summary: Researchers face challenges in developing treatments for emerging and re-emerging epidemic infections. Drug repurposing is a reliable strategy for discovering new antiviral agents quickly and reducing the need for clinical trials.
DRUG DISCOVERY TODAY
(2022)
Review
Biochemistry & Molecular Biology
Mir Aroosa, Jonaid Ahmad Malik, Sakeel Ahmed, Onur Bender, Nafees Ahemad, Sirajudheen Anwar
Summary: This review examines the anticancer properties of antiepileptic drugs and their connection to cancer and epileptic pathways. Drugs that have shown positive results in clinical trials and preclinical studies are analyzed. The search for alternative, efficient cancer treatments is crucial due to factors like drug resistance, tumor heterogeneity, and cost. Drug repurposing methods, aided by genomic and proteomic advancements, offer potential in the discovery of new antitumor molecules. The potential of antiepileptic drugs, such as valproic acid, oxcarbazepine, lacosamide, lamotrigine, and levetiracetam, in different cancers and brain tumor progression is summarized. While antiepileptic drugs may be a promising option for adjuvant cancer therapy, further investigation is needed through clinical trials.
MOLECULAR BIOLOGY REPORTS
(2023)
Review
Oncology
Ahmed Olatunde, Manisha Nigam, Rahul Kunwar Singh, Abhaya Shikhar Panwar, Abdulwahab Lasisi, Fahad A. Alhumaydhi, Vijay Jyoti Kumar, Abhay Prakash Mishra, Javad Sharifi-Rad
Summary: Cancer management often involves chemotherapy, surgery, and radiotherapy, but chemotherapy can be cytotoxic to normal cells and lead to drug resistance. Antidiabetic drugs such as sulfonylureas, biguanides, and thiazolidinediones have shown beneficial effects in cancer treatment, despite potential risks like pancreatic cancer development.
CANCER CELL INTERNATIONAL
(2021)
Article
Immunology
Amar Ajmal, Arif Mahmood, Chandni Hayat, Mohammed Ageeli Hakami, Bader S. Alotaibi, Muhammad Umair, Ashraf N. Abdalla, Ping Li, Pei He, Abdul Wadood, Junjian Hu
Summary: Monkeypox is a zoonotic disease caused by monkeypox virus, transmitted through respiratory droplets, skin lesions, and body fluids. The study aims to identify potential drugs using computational methods.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Oncology
Michael A. Sun, Rui Yang, Heng Liu, Wenzhe Wang, Xiao Song, Bo Hu, Nathan Reynolds, Kristen Roso, Lee H. Chen, Paula K. Greer, Stephen T. Keir, Roger E. McLendon, Shi-Yuan Cheng, Darell D. Bigner, David M. Ashley, Christopher J. Pirozzi, Yiping He
Summary: In this study, researchers discovered that clemastine, a non-oncology drug for allergy relief, can inhibit the proliferation and promote differentiation of brain tumor-initiating cells (BTICs). They also identified the essential role of Emopamil-binding protein (EBP) in maintaining the BTIC population. These findings provide valuable insights for developing new treatments for glioblastoma.
Review
Pharmacology & Pharmacy
Josef Jampilek
Summary: Infections pose an escalating global threat due to the alarming rise in resistant microbial pathogens. This review summarizes the causes of antimicrobial resistance, discusses various approaches to the discovery of new anti-infective drugs, and focuses on the strategy of drug repurposing, offering critical remarks on the repurposing of non-antibiotics. A comprehensive overview of drugs tested for their antimicrobial activity is provided to support existing anti-infective therapeutics.
DRUG DISCOVERY TODAY
(2022)
Review
Immunology
Samreen Fatima, Ashima Bhaskar, Ved Prakash Dwivedi
Summary: Tuberculosis is a deadly infectious disease caused by Mycobacterium tuberculosis. Current treatment involves a combination of antibiotics for 6 months, but limitations such as toxicity and long duration make adherence challenging, leading to drug resistance. The development of new TB drugs is crucial to combat drug resistance and shorten treatment duration, but the process is time-consuming and costly. Repurposing existing drugs for other diseases shows promise in targeting multiple pathways to reduce the risk of drug resistance and has potential as adjunct therapies against TB.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tania Lourenco, Nuno Vale
Summary: Prostate cancer is the second most common cancer in men worldwide and a leading cause of death. Standard treatments face issues like side effects and resistance, highlighting the need for drugs that can fill these gaps. This review compiles drugs that can be repurposed for prostate cancer treatment, categorizing them based on their pharmacotherapeutic groups and discussing their mechanisms of action.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Nick Cunniffe, Khue Anh Vuong, Debbie Ainslie, David Baker, Judy Beveridge, Sorrel Bickley, Patrick Camilleri, Matthew Craner, Denise Fitzgerald, Alerie G. de la Fuente, Gavin Giovannoni, Emma Gray, Lorraine Hazlehurst, Raj Kapoor, Ranjit Kaur, David Kozlowski, Brooke Lumicisi, Don Mahad, Bjoern Neumann, Alan Palmer, Luca Peruzzotti-Jametti, Stefano Pluchino, Jennifer Robertson, Alan Rothaul, Lyndsey Shellard, Kenneth J. Smith, Alastair Wilkins, Anna Williams, Alasdair Coles
Summary: This study established a standardized approach for identifying candidate drugs for repurposing in the treatment of progressive MS. Through expert review and scoring, four treatments were recommended for immediate testing in progressive MS, with additional treatments prioritized for further consideration. This approach offers new possibilities for the treatment of patients with progressive MS.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Rawan Nehme, Rawan Hallal, Maya El Dor, Firas Kobeissy, Fabrice Gouilleux, Frederic Mazurier, Kazem Zibara
Summary: Drug repurposing has shown great potential in cancer treatment, with Acriflavine (ACF) being an FDA approved molecule that has wide-ranging antimicrobial and anticancer effects, especially in Chronic Myeloid Leukemia (CML) therapy.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Tianduanyi Wang, Otto I. Pulkkinen, Tero Aittokallio
Summary: Most drug molecules have the ability to modulate multiple target proteins, which can lead to both therapeutic effects and unwanted side effects. Evaluating the selectivity of a compound is an important factor in drug development and repurposing efforts. Traditional methods for characterizing selectivity fall short in quantifying how selective a compound is against a particular target protein. In this study, we propose an optimization-based selectivity scoring method that allows for the identification of potent and selective compounds against given kinase targets. We demonstrate the effectiveness of this method in finding highly selective compounds in computational experiments using a large-scale kinase inhibitor dataset.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Agriculture, Dairy & Animal Science
Antonio Giuliano, Rodrigo S. Horta, Rafael A. M. Vieira, Kelly R. Hume, Jane Dobson
Summary: Repurposing drugs in oncology involves using off-label drugs that are licensed for non-oncological medical conditions to treat cancer. This approach offers the advantage of using already commercialized drugs with known safety profiles and mechanisms of action. This review summarizes the benefits and challenges of repurposing anti-cancer drugs, discusses relevant studies in small animal oncology, and proposes potential drugs for clinical investigation in dogs and cats.
Review
Biochemistry & Molecular Biology
Catarina Moura, Nuno Vale
Summary: Dopamine is a neurotransmitter that regulates cognitive and emotional processes in the brain. Its role in cancer is uncertain, but it interacts with receptors in tumor cells and influences cellular processes such as proliferation and migration. Drugs developed for other purposes have been explored for potential cancer treatment, but the role of dopamine in this context needs further clarification.
Article
Pharmacology & Pharmacy
Marco Sisignano, Philip Gribbon, Gerd Geisslinger
Summary: Around 20% of the American population suffer from chronic pain, posing a major challenge for global healthcare systems. Existing therapies have low efficacy, but research suggests that some drugs originally developed for other conditions may have analgesic effects.
Review
Biochemistry & Molecular Biology
Izabela Rumienczyk, Maria Kulecka, Malgorzata Statkiewicz, Jerzy Ostrowski, Michal Mikula
Summary: Despite no approved treatment for sepsis, preclinical studies have shown the potential of oncology drugs in improving sepsis. Further testing of standard and oncology drug combinations holds promise for better clinical outcomes in sepsis.
Article
Immunology
Ahmad Mourad, Nicholas A. Turner, Arthur W. Baker, Nwora Lance Okeke, Shanti Narayanasamy, Robert Rolfe, John J. Engemann, Gary M. Cox, Jason E. Stout
Summary: In June 2020, increases in SARS-CoV-2 cases in the US were found to be associated with densely populated metropolitan areas, higher percentages of black residents, and counties that supported the Republican candidate in the 2016 presidential election. These sociodemographic and political factors were independently linked to rising case counts. Addressing social disparities and political beliefs is crucial for pandemic control efforts.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Oncology
George Sharbeen, Joshua A. McCarroll, Anouschka Akerman, Chantal Kopecky, Janet Youkhana, John Kokkinos, Jeff Holst, Cyrille Boyer, Mert Erkan, David Goldstein, Paul Timpson, Thomas R. Cox, Brooke A. Pereira, Jessica L. Chitty, Sigrid K. Fey, Arafath K. Najumudeen, Andrew D. Campbell, Owen J. Sansom, Rosa Mistica C. Ignacio, Stephanie Naim, Jie Liu, Nelson Russia, Julia Lee, Angela Chou, Amber Johns, Anthony J. Gill, Estrella Gonzales-Aloy, Val Gebski, Yi Fang Guan, Marina Pajic, Nigel Turner, Minoti Apte, Thomas P. Davis, Jennifer P. Morton, Koroush S. Haghighi, Jorjina Kasparian, Benjamin J. McLean, Yordanos F. Setargew, Phoebe A. Phillips
Summary: High expression of SLC7A11 in human PDAC tumor stroma, independently prognostic of poorer overall survival. The study demonstrates that PDAC-derived CAFs are highly dependent on SLC7A11 for cystine uptake and glutathione synthesis. Inhibition of SLC7A11 decreases CAF proliferation, reduces their resistance to oxidative stress, and inhibits their ability to support PDAC cell growth.
Article
Cell Biology
Yang Emma Li, Yichang Wang, Ximing Du, Tizhong Zhang, Hoi Yin Mak, Sarah E. Hancock, Holly McEwen, Elvis Pandzic, Renee M. Whan, Yvette Celine Aw, Ivan E. Lukmantara, Yiqiong Yuan, Xiuju Dong, Anthony Don, Nigel Turner, Shiqian Qi, Hongyuan Yang
Summary: TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum, regulating the formation of lipid droplets and lipoproteins, and playing a crucial role in viral infection. They act as phospholipid scramblases, affecting the cellular distribution of cholesterol and phosphatidylserine.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Oncology
Qian Wang, Yi Fang Guan, Sarah E. Hancock, Kanu Wahi, Michelle van Geldermalsen, Blake K. Zhang, Angel Pang, Rajini Nagarajah, Blossom Mak, Natasha Freidman, Lisa G. Horvath, Nigel Turner, Jeff Holst
Summary: Glutamine is a critical nutrient in cancer, especially in prostate cancer; and Guanosine monophosphate synthetase (GMPS) plays a significant role in de novo purine biosynthesis pathway. High expression of GMPS is associated with decreased survival rates in prostate cancer, and inhibition or knockdown of GMPS can significantly decrease cell growth in prostate cancer cells. These findings highlight the importance of glutamine metabolism and suggest GMPS as a potential therapeutic target in prostate cancer.
JOURNAL OF PATHOLOGY
(2021)
Article
Medicine, Research & Experimental
Vaishali Jayashankar, Elizabeth Selwan, Sarah E. Hancock, Amandine Verlande, Maggie O. Goodson, Kazumi H. Eckenstein, Giedre Milinkeviciute, Brianna M. Hoover, Bin Chen, Angela G. Fleischman, Karina S. Cramer, Stephen Hanessian, Selma Masri, Nigel Turner, Aimee L. Edinger
Summary: Compounds targeting mitochondrial dynamics are ineffective at blocking ceramide-induced fission, while targeting endolysosomal trafficking events can rapidly and effectively prevent disruptions in mitochondrial form and function caused by ceramide.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Louise K. Metcalfe, Peter R. Shepherd, Greg C. Smith, Nigel Turner
Summary: The Arg457Gln variant in the CREBRF gene is associated with excess body weight and paradoxical reduction in diabetes risk in Pacific/Oceanic populations. A mouse model with the Crebrf Arg458Gln variant showed limited phenotypic effects, suggesting a need to reconsider the mechanistic link between CREBRF function and obesity and diabetes risks in variant allele carriers.
Article
Multidisciplinary Sciences
Amelia K. Fotheringham, Samantha M. Solon-Biet, Helle Bielefeldt-Ohmann, Domenica A. McCarthy, Aisling C. McMahon, Kari Ruohonen, Isaac Li, Mitchell A. Sullivan, Rani O. Whiddett, Danielle J. Borg, Victoria C. Cogger, William O. Ballard, Nigel Turner, Richard G. Melvin, David Raubenheimer, David G. Le Couteur, Stephen J. Simpson, Josephine M. Forbes
Summary: This study on mice found that protein intake has the greatest impact on kidney function, with chronic low protein intake leading to decreased glomerular filtration rates and structural injury in the kidneys, independent of cardiometabolic risk factors.
Article
Biochemistry & Molecular Biology
Brenna Osborne, Jane Reznick, Lauren E. Wright, David A. Sinclair, Gregory J. Cooney, Nigel Turner
Summary: This study investigated the effects of liver-specific SIRT3 overexpression on mitochondrial function and metabolism. The results showed that overexpression of SIRT3 increased oxygen consumption and reduced triglyceride accumulation. However, increasing hepatic SIRT3 had limited overall benefits during the development of diet-induced insulin resistance.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Margaret A. Mouat, Brendan P. Wilkins, Eileen Ding, Hemna Govindaraju, James L. J. Coleman, Robert M. Graham, Nigel Turner, Nicola J. Smith
Summary: The deletion of GPR37L1 does not significantly affect glucose handling, body weight, and fat mass in mice. However, Gpr37l1(-/-) mice show lower fat mass accumulation and higher ambulatory activity during night hours.
Article
Biochemistry & Molecular Biology
Samuel G. Towarnicki, Neil A. Youngson, Susan M. Corley, Jus C. St John, Richard G. Melvin, Nigel Turner, Margaret J. Morris, J. William O. Ballard
Summary: Studies have shown that ancestral life experiences, particularly stress and diet, can influence the growth, metabolism, and behavior of future generations. This research focuses on the non-genetic inheritance between fertilization and adulthood, revealing that ancestral dietary macronutrient composition and quantity can impact the developmental timing of descendants through changes in specific signaling pathways.
Article
Genetics & Heredity
Gabriella Assante, Sriram Chandrasekaran, Stanley Ng, Aikaterini Tourna, Carolina H. Chung, Kowsar A. Isse, Jasmine L. Banks, Ugo Soffientini, Celine Filippi, Anil Dhawan, Mo Liu, Steven G. Rozen, Matthew Hoare, Peter Campbell, J. William O. Ballard, Nigel Turner, Margaret J. Morris, Shilpa Chokshi, Neil A. Youngson
Summary: The research demonstrates that metabolically driven histone hyperacetylation in steatotic hepatocytes can increase DNA damage, thus initiating the development of HCC.
Article
Biochemistry & Molecular Biology
Sarah E. Hancock, Eileen Ding, Emma Johansson Beves, Todd Mitchell, Nigel Turner
Summary: Recent advances in single-cell genomics and transcriptomics have greatly improved our understanding of cellular heterogeneity, but single-cell lipidomics methods have lagged behind. However, we have developed a method combining fluorescence-assisted cell sorting and shotgun lipidomics that allows us to detect and quantify a wide range of phosphatidylcholine and sphingomyelin species from single cells. This method can distinguish between different cell lineages and detect subtle differences in the lipidome between cell lines of the same cancer type. It can also be used in conjunction with other single-cell technologies to provide comprehensive multi-omics data on cells with similar phenotypes, advancing our knowledge on cellular heterogeneity.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Endocrinology & Metabolism
Brenna Osborne, Lauren E. Wright, Amanda E. Brandon, Ella Stuart, Lewin Small, Joris Hoeks, Patrick Schrauwen, David A. Sinclair, Magdalene K. Montgomery, Gregory J. Cooney, Nigel Turner
Summary: This study investigated whether specific overexpression of SIRT3 in skeletal muscle could prevent high-fat diet-induced muscle insulin resistance. The results showed that overexpression of SIRT3 did not alleviate muscle insulin resistance induced by high-fat diet and intramuscular triglyceride content was increased. These findings indicate that muscle-specific overexpression of SIRT3 has only minor effects on the acute development of skeletal muscle insulin resistance in high-fat-fed rats.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Adam J. Lawther, Jerzy Zieba, Zhiming Fang, Teri M. Furlong, Illya Conn, Hemna Govindaraju, Laura L. Y. Choong, Nigel Turner, Khawar Sohail Siddiqui, Wallace Bridge, Sam Merlin, Tzipi Cohen Hyams, Murray Killingsworth, Valsamma Eapen, Raymond A. Clarke, Adam K. Walker
Summary: Mitochondrial dysfunction is strongly associated with autism spectrum disorder (ASD), and the IMMP2L gene is linked to autism inheritance. By developing an Immp2lKD knockout mouse model, the researchers found that Immp2l(KD) -/- KO mice did not show any differences in the core behavioral symptoms of ASD, but they exhibited increased auditory stimulus-driven instrumental behavior and amphetamine-induced locomotion. The researchers also discovered that the ROS levels were lowered in the new Immp2l(KD) -/- KO mice, contrary to previous studies on Immp2l-deficient mouse models, and these mice did not display oxidative stress-related phenotypes.
Article
Cell Biology
Indra Heckenbach, Garik V. Mkrtchyan, Michael Ben Ezra, Daniela Bakula, Jakob Sture Madsen, Malte Hasle Nielsen, Denise Oro, Brenna Osborne, Anthony J. Covarrubias, M. Laura Idda, Myriam Gorospe, Laust Mortensen, Eric Verdin, Rudi Westendorp, Morten Scheibye-Knudsen
Summary: A deep learning predictor based on nuclear morphology can identify senescent cells and is associated with health outcomes in humans.
