UNC Eshelman School of Pharmacy

FRIDAY, Aug. 2, 2024 -- Recently, there was an increase in availability of naloxone after it was approved to be sold as an over-the-counter (OTC) medication, according to a study published online July 26 in JAMA Health Forum . Grace T. Marley, Pharm.D., from the UNC Eshelman School of Pharmacy in Chapel Hill, North Carolina, and colleagues examined whether the accessibility and cost of naloxone at North Carolina community pharmacies changed after OTC naloxone became available. Data were collected from shoppers at 192 pharmacies in a longitudinal survey study. Data were collected from March to April 2023 (before OTC naloxone could be sold at pharmacies) and from November 2023 to January 2024 (after naloxone was sold at pharmacies). The researchers found that from before to after naloxone availability at pharmacies, there was an increase in same-day naloxone availability from 42.2 to 57.8 percent. The mean quoted out-of-pocket cost decreased from $90.93 to $62.67 pre- to post-OTC availability. In both the pre- and post-OTC phases, mean costs were significantly higher at independent pharmacies than chain pharmacies ($109.47 versus $86.40 and $77.59 versus $57.74, respectively). In the pre-OTC phase, there was no difference seen in out-of-pocket costs by urbanicity, while mean costs were significantly higher at suburban and rural versus urban pharmacies in the post-OTC phase ($88.67 and $65.43, respectively, versus $53.58). "This study found elevated out-of-pocket costs for naloxone at independent pharmacies compared with chain pharmacies and in rural and suburban pharmacies compared with urban pharmacies," the authors write. "Overall, future work should evaluate OTC naloxone pricing strategies at pharmacies and evaluate methods to increase its same-day availability." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Researchers have determined that a protein prediction technology can yield accurate results in the hunt to efficiently find the best possible drug candidates for many conditions. Artificial intelligence (AI) has numerous applications in healthcare, from analyzing medical imaging to optimizing the execution of clinical trials, and even facilitating drug discovery. AlphaFold2, an artificial intelligence system that predicts protein structures, has made it possible for scientists to identify and conjure an almost infinite number of drug candidates for the treatment of neuropsychiatric disorders. However recent studies have sown doubt about the accuracy of AlphaFold2 in modeling ligand binding sites, the areas on proteins where drugs attach and begin signaling inside cells to cause a therapeutic effect, as well as possible side effects. In a new paper, Bryan Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology and director of the NIMH Psychoactive Drug Screening Program at the University of North Carolina School of Medicine, and colleagues at UCSF, Stanford and Harvard determined that AlphaFold2 can yield accurate results for ligand binding structures, even when the technology has nothing to go off of. Their results were published in Science. "Our results suggest that AF2 structures can be useful for drug discovery," said Roth, senior author who holds a joint appointment at the UNC Eshelman School of Pharmacy. "With a nearly infinite number of possibilities to create drugs that hit their intended target to treat a disease, this sort of AI tool can be invaluable." AlphaFold2 and Prospective Modeling Much like weather forecasting or stock market prediction, AlphaFold2 works by pulling from a massive database of known proteins to create models of protein structures. Then, it can simulate how different molecular compounds (like drug candidates) fit into the protein's binding sites and produce wanted effects. Researchers can use the resulting combinations to better understand protein interactions and create new drug candidates. To determine the accuracy of AlphaFold2, researchers had to compare the results of a retrospective study against that of a prospective study. A retrospective study involves researchers feeding the prediction software compounds they already know bind to the receptor. Whereas, a prospective study requires researchers to use the technology as a fresh slate, and then feed the AI platform information about compounds that may or may not interact with the receptor. Researchers used two proteins, sigma-2 and 5-HT2A, for the study. These proteins, which belong to two different protein families, are important in cell communication and have been implicated in neuropsychiatric conditions such as Alzheimer's disease and schizophrenia. The 5-HT2A serotonin receptor is also the main target for psychedelic drugs which show promise for treating a large number of neuropsychiatric disorders. Roth and colleagues selected these proteins because AlphaFold2 had no prior information about sigma-2 and 5-HT2A or the compounds that might bind to them. Essentially, the technology was given two proteins for which it wasn't trained on -- essentially giving the researchers a "blank slate." First, researchers fed the AlphaFold system the protein structures for sigma-2 and 5-HT2A, creating a prediction model. Researchers then accessed physical models of the two proteins that were produced using complex microscopy and x-ray crystallography techniques. With a press of a button, as many as 1.6 billion potential drugs were targeted to the experimental models and AlphaFold2 models. Interestingly, every model had a different drug candidate outcome. Successful Hit Rates Despite the models having differing results, they show great promise for drug discovery. Researchers determined that the proportion of compounds that actually altered protein activity for each of the models were around 50% and 20% for the sigma-2 receptor and 5-HT2A receptors, respectively. A result greater than 5% is exceptional. Out of the hundreds of millions of potential combinations, 54% of the drug-protein interactions using the sigma-2 AlphaFold2 protein models were successfully activated through a bound drug candidate. The experimental model for sigma-2 produced similar results with a success rate of 51%. "This work would be impossible without collaborations among several leading experts at UCSF, Stanford, Harvard, and UNC-Chapel Hill," Roth said. "Going forward we will test whether these results might be applicable to other therapeutic targets and target classes."

-- Since 2018, The Mark Foundation ASPIRE program has provided more than $48M to fund 118 awards for high-risk, high-reward research that cuts across multiple cancer types and scientific disciplines. NEW YORK, Nov. 15, 2023 /PRNewswire/ -- The Mark Foundation for Cancer Research announced 16 outstanding projects in its latest class of ASPIRE awards, granting more than $5 million for research that aims to answer key feasibility and proof-of-concept questions in an accelerated time frame, and scaling for impact based upon initial success. The high-risk nature of these projects, often based on new ideas that have generated limited preliminary data, tends to place them outside the scope of other funding opportunities. These new awards cover research into multiple types of adult and pediatric cancers, encompassing both solid tumors and blood cancers. Of note, two of the projects result from a request for proposals following a Mark Foundation scientific workshop on pediatric brain tumors, which convened worldwide experts to dream up novel solutions to the critical problem that brain tumors kill more children than any other cancer. The Mark Foundation's commitment to interdisciplinary research and global collaboration is also embodied by these new grants, with many different fields of study represented including genetics, chemical biology, artificial intelligence (AI), immuno-oncology, biophysics, and cancer prevention. For example, two of the projects will apply state-of-the-art technologies in AI and structural biology to study the T-cell receptor, a signaling node that is key for successful cancer immunotherapies. Another project brings together laboratories from the United Kingdom and Australia working on lung cancer and breast cancer to collaborate on cancer prevention and protection. "These ASPIRE awards will enable trailblazing approaches to help solve some of the biggest challenges in cancer research today," said Ryan Schoenfeld, CEO, The Mark Foundation. "I'm excited to see these projects embracing the high-risk / high-reward spirit of the program and covering such a broad range of important scientific questions and different cancer types that represent areas of high unmet need for patients." Launched in 2018, The Mark Foundation ASPIRE Award program has provided 118 grants totaling over $48 million across 63 different research institutions in 12 countries. David Allman, PhD, and Dan Vogl, MD, MSCE, University of Pennsylvania Perelman School of Medicine Survival pathways in multiple myeloma Regina Barzilay, PhD, and Tyler Jacks, PhD, Massachusetts Institute of Technology AI-driven modeling of T-cell receptors Madhav Dhodapkar, MBBS, Winship Cancer Institute of Emory University; Richard Flavell, PhD and Noah Palm, PhD, Yale University Understanding and targeting microbial triggers for myeloma Courtney Hodges, PhD, and Damian Young, PhD, Baylor College of Medicine; Nathaniel Hathaway, PhD, UNC Eshelman School of Pharmacy Chemical-induced proximity for control of STAT transcription factor networks Darrell Irvine, PhD, and Dane Wittrup, PhD, Massachusetts Institute of Technology Induction of tumor-eradicating systemic immunity via leukocyte-targeted cytokine therapy Taha Merghoub, PhD, and Jedd Wolchok, MD, PhD, Weill Cornell Medicine Investigating novel KRAS inhibitors effects on the tumor-immune responses and integration of KRAS inhibition Jim Olson, MD, PhD, and Surojit Sarkar, PhD, Seattle Children's Research Institute PD-L1 bispecific & CXCL10 armored CARs for Diffuse Midline Gliomas Owen Sansom, PhD, Cancer Research UK Scotland Institute; Sabine Tejpar, MD, PhD, KU/UZ Leuven; Ramanuj DasGupta, PhD, Genome Institute of Singapore Defining the origin, evolution and therapeutic vulnerabilities of metaplastic colorectal cancer Sriram Venneti, MD, PhD, University of Michigan, Ann Arbor; Michael Taylor, MD, PhD, Baylor College of Medicine; Elaine Mardis, PhD, Nationwide Children's Hospital Defining pre-cancerous potential of persistent rhombic lip (PeRL) to develop biomarkers for group 3/4 medulloblastoma Andrea Ventura, MD, PhD, Memorial Sloan Kettering Cancer Center Defining the Roles Of ecDNAs In Cancer Initiation and Progression Jun Wang, PhD, and Iannis Aifantis, PhD, NYU Langone Health and its Perlmutter Cancer Center Antigen Presentation Inhibitors for Cancer Immunotherapy Thomas Walz, PhD, and Ryan Notti, MD, PhD, Rockefeller University Structural biochemistry of T-cell receptor activation Christina Woo, PhD, Harvard University Discovery of E3 ligase substrate adapters of overlooked forms of protein damage ASPIRE II awards: Stephen Jackson, PhD, and Samah Awwad, PhD, University of Cambridge Dissecting molecular mechanism(s) of ATR-inhibitor and CHK1-inhibitor sensitivity and resistance Bennie Lemmens, PhD, and Jiri Bartek, MD, PhD, Karolinska Institutet Redefining cancer drug resistance and replication timing at nucleotide and nanoscale resolution Charles Swanton, MD, PhD, The Francis Crick Institute and Sherene Loi, MD, PhD, University of Melbourne Tumor promotion and protection About The Mark Foundation for Cancer Research The Mark Foundation for Cancer Research, a charitable organization based in New York City, actively partners with scientists around the world to accelerate research that will transform the prevention, diagnosis, and treatment of cancer. Since 2017, The Mark Foundation has awarded more than $200 million in grants to over 100 academic institutions across 13 countries, with research programs focusing on early career support, team science collaboration, new technology innovation, and therapeutics discovery. Additionally, The Mark Foundation maintains a growing portfolio of investments in early-stage cancer diagnostics and therapeutics companies, including several that have transitioned from grantee projects into commercial development. To learn more please visit . Contact: Linda Heaney [email protected] SOURCE The Mark Foundation for Cancer Research