Chemicals and Drugs Commons^™

Molecular Docking Of The Interaction Between Citrus Amblycarpa Extract Contents And Inflammatory Proteins Of Hepatic Steatosis, Lena Rosida, Dewi Indah Noviana Pratiwi, Roselina Panghiyangani, Juliyatin Putri Utami, Nasrul Idhafi, Muhammad Febriansyah, Andi Azizah Maulidia Budiarman

Makara Journal of Science

Citrus amblycarpa possesses various pharmacological activities, such as antioxidant, anticancer, antitumor, hepatoprotective, anti-inflammatory, antidiabetic, antiviral, antibacterial, and antifungal. The main active compounds in C. amblycarpa (including gamma (γ)-aminobutyric acid [GABA], hesperidin, naringin, neoeriocitrin, poncirin, quercetin, and rutin) show potential to interact with the inflammatory proteins in hepatic steatosis (such as nuclear factor kappa beta [NF-kB], tumor necrosis alpha [TNF-alpha], interleukin-6 [IL-6], c-Jun NH2-terminal kinase [JNK], and adiponectin). Molecular docking simulations were performed using Swiss Dock (http://www.swissdock.ch/), and analysis and visualization were conducted using Discovery Studio 4.1. Rutin, poncirin, hesperidin, and neoeriocitrin exhibit high affinities to NF-κB, TNF-alpha, IL-6, and adiponectin …

A Homogeneous Time-Resolved Fluorescence Screen To Identify Sirt2 Deacetylase And Defatty-Acylase Inhibitors, Jie Yang, Joel Cassel, Brian C Boyle, Daniel Oppong, Young-Hoon Ahn, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Human sirtuin-2 (SIRT2) has emerged as an attractive drug target for a variety of diseases. The enzyme is a deacylase that can remove chemically different acyl modifications from protein lysine residues. Here, we developed a high-throughput screen based on a homogeneous time-resolved fluorescence (HTRF) binding assay to identify inhibitors of SIRT2's demyristoylase activity, which is uncommon among many ligands that only affect its deacetylase activity. From a test screen of 9600 compounds, we identified a small molecule that inhibited SIRT2's deacetylase activity (IC50 = 7 μM) as well as its demyristoylase activity (IC50 = 37 μM). The inhibitor was composed …

Ephrin-B2 Promotes Nociceptive Plasticity And Hyperalgesic Priming Through Ephb2-Mnk-Eif4e Signaling In Both Mice And Humans, Eric David, Muhammad Saad Yousuf, Hao-Ruei Mei, Ashita Jain, Sharada Krishnagiri, Hajira Elahi, Rupali Venkatesan, Kolluru Srikanth, Gregory Dussor, Matthew Dalva, Theodore Price

Department of Neuroscience Faculty Papers

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines …

Association Of C-Reactive Protein/Albumin Ratio With Mortality In Patients With Traumatic Brain Injury: A Systematic Review And Meta-Analysis, Yuyang Liu, Yaheng Tan, Jun Wan, Qiwen Chen, Yuxin Zheng, Wenhao Xu, Peng Wang, Weelic Chong, Xueying Yu, Yu Zhang

Department of Medical Oncology Faculty Papers

Objective: This study examines the C-reactive protein (CRP)/albumin ratio (CAR) as an inflammation-based prognostic score for predicting mortality in patients with Traumatic Brain Injury (TBI). Methods: We systematically searched the electronic databases PubMed, Embase, and Cochrane up to February 2024. Our inclusion criteria encompassed studies investigating CAR-predicted mor- tality in patients with TBI. We calculated the Odds Ratio (OR) and associated 95 % confidence intervals (95 % CI) using a random-effects model. Quality assessment of the included studies was appraised using a Newcastle–Ottawa scale. Results: A total of five studies comprising 1040 patients were included in this meta-analysis. The pooled …

Riluzole For Degenerative Cervical Myelopathy: A Secondary Analysis Of The Csm-Protect Trial, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Jetan H. Badhiwala, Henry Ahn, H. Francis Farhadi, Christopher I. Shaffrey, Ahmad Nassr, Praveen Mummaneni, Paul M. Arnold, Bradley Jacobs, K. Daniel Riew, Michael Kelly, Darrel S. Brodke, Alexander R. Vaccaro, Alan S. Hilibrand, Jason Wilson, James S. Harrop, S. Timm Yoon, Kee D. Kim, Daryl R. Fourney, Carlo Santaguida, Eric M. Massicotte, Peng Huang

School of Medicine Faculty Publications

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical …

Amiodarone-Induced Lung Toxicity: An Underrecognized And Fatal Presentation, Andrew Takla, Fahad Eid, Hina Ukrani, Moghniuddin Mohamed, Elizabeth Lee

Advances in Clinical Medical Research and Healthcare Delivery

Amiodarone, a widely utilized antiarrhythmic drug, poses a significant risk of amiodarone-induced lung toxicity (ALT) in up to 10% of patients and can be fatal. This report presents the diagnostic challenges associated with ALT, given its non-specific clinical and radiological presentation. Clinicians should maintain a high index of suspicion for potential ALT, especially in patients with progressive respiratory failure despite optimization of other potential causes such as CHF. The mainstay of treatment is discontinuing amiodarone and initiating steroids. However, outcomes can remain unpredictable, emphasizing the need for heightened awareness and regular monitoring of patients on amiodarone therapy.

Mechanistic Study Of Antimicrobial Effectiveness Of Cyclic Amphipathic Peptide [R4W4] Against Methicillin-Resistant Staphylococcus Aureus Clinical Isolates, Ajayi David Akinwale, Keykavous Parang, Rakesh Kumar Tiwari, Jason Yamaki

Pharmacy Faculty Articles and Research

Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R₄W₄] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R₄W₄] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R₄W₄] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but …

Studies In Natural Product-Inspired Complex Molecule Synthesis: Synthesis Of 26-Norpentacyclic Triterpenoids And Anhydroryanodol, Zachary D. Stempel

Dartmouth College Ph.D Dissertations

Natural products have long served as a stimulus for growth and innovation to advance the field of organic chemistry. This thesis describes efforts in complex molecule synthesis that demonstrate the broad value of programs in natural product total synthesis and natural product-inspired function-oriented synthesis. The first part of this thesis describes a function-oriented synthesis approach to pentacyclic triterpenoids through design of a simplified 26-norpentacyclic triterpenoid platform to promote future medicinal exploration in this area. These studies yielded a divergent asymmetric synthesis of 26-norgermanicol and 26-norlupeol as well as the discovery of a new class of androgen receptor antagonist that is …

Long-Term Survival Follow-Up For Tebentafusp In Previously Treated Metastatic Uveal Melanoma, Joseph Sacco, Richard Carvajal, Marcus Butler, Alexander N Shoushtari, Jessica Hassel, Alexandra Ikeguchi, Leonel Hernandez-Aya, Paul Nathan, Omid Hamid, Josep Piulats, Matthew Rioth, Douglas B Johnson, Jason Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Chris Holland, Takami Sato

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

PATIENTS AND METHODS: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman

Lux et Fides: A Journal for Undergraduate Christian Scholars

DNA methylation occurring on the O⁶ position of guanine has been linked to the formation of cancer. DNA complexes with O⁶-methylated guanine have been studied experimentally, yet questions remain concerning the carcinogenic properties of O⁶-methylguanine. This present research explored the interaction between O⁶-methylguanine and its potential nucleobase pairs of cytosine and adenine in hopes of elucidating the mutagenic characteristics of O⁶-methylguanine. A variety of computational methods including Density Functional Theory (DFT), Symmetry Adapted Perturbation Theory (SAPT), Noncovalent Interaction (NCI) analysis, and Natural Bond Orbital (NBO) analysis were employed to comprehensively probe …

Hairy Tongue Associated With The Use Of Baricitinib Therapy For Ophiasis Pattern Alopecia Areata, Anthony Gaspari

Department of Dermatology and Cutaneous Biology Faculty Papers

We report a case of hairy tongue that developed in a young Caucasian
/="/">woman during systemic baricitinib therapy for severe alopecia areata.
/="/">Because she experienced good clinical regrowth of her hair during
/="/">treatment, she did not want to interrupt therapy. We recommended she
/="/">use a toothbrush to debride her tongue on a daily basis, which was
/="/">successful. Hairy tongue most commonly occurs in elderly, debilitated
/="/">males with poor oral hygiene. It is thought to occur because of overgrowth
/="/">of chromogenic bacteria and/or yeast on the tongue. This unusual side
/="/">effect during baricitinib …

Understanding The Relationship Between [Atp], Growth Rate, And Inoculum Effect In Β-Lactamase Producing Bacteria, Ariane R. Kalifa

All HCAS Student Capstones, Theses, and Dissertations

2.8 million Americans are infected with antibiotic-resistant bacteria on an annual basis, leading to increased mortality and morbidity. With the incidence of infection due to antibiotic-resistant bacteria on the rise, it is critical to understand the mechanisms bacteria use to resist antibiotics. The inoculum effect (IE) is a phenomenon that has been observed for many antibiotics and bacterial species. In IE, the density of the bacterial population determines the minimum inhibitory concentration of the antibiotic (MIC) of an antibiotic; as the density of the bacterial population increases, the MIC increases. IE is highly prevalent in bacteria that express β-lactamases where …

Transport Of The Fluorescent Substrate Asp+ By Organic Cation Transporter-3 In Human Corneal Epithelial Cells, Jeremy Laws

Theses & Dissertations

ABSTRACT

Organic cation transporter-3 (OCT3) is expressed abundantly throughout the body, but little is known about the presence of these transporters within the eye and, more specifically, the cornea epithelium. An extensive library of compounds interacts with OCT3, including the fluorescent molecule ASP⁺ and metformin. Metformin is an OCT3 substrate and antidiabetic medication that can lower the risk of eye-related diseases like keratopathy and retinopathy linked to hyperglycemia. Utilizing high throughput microplate assays in a human cornea epithelial cell line (HCE-S), the time-dependent saturation of ASP⁺ uptake and the competition of ASP⁺ uptake by corticosterone (CORT), a …

April / May / June 2024, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the April, May, and June issue of Rural Rocks from the SWOSU College of Pharmacy.

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma, Angela Alnemri, Sruti Tekumalla, Annie Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David Cognetti, Joseph Curry, Athanassios Argiris, Alban Linnenbach, Andrew South, Larry Harshyne, Jennifer Johnson, Adam Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

The Utilisation Of Mushroom Leftovers, Oats, And Lactose-Free Milk Powder For The Development Of Geriatric Formulation, Snigdha Paul, Ravinder Kaushik, Shuchi Upadhyay, Ansab Akhtar, Prince Chawla, Naveen Kumar, Saurabh Sharma, Pooja Rani

School of Medicine Faculty Publications

This study aims to focus on developing a food supplement for the geriatric population using disposal mushrooms, oats, and lactose-free milk powder. Lactose intolerance is most common in older adults, raising the demand for lactose-free foods. One of the major global challenges currently faced by humankind is food waste (FW). Most of the food that is produced for human consumption has not been utilized completely (1/3rd-1/2 unutilized), resulting in agricultural food waste. Mushrooms are highly valuable in terms of their nutritional value and medicinal properties; however, a significant percentage of mushroom leftovers are produced during mushroom production that do not …

Hyperoxia-Induced Mir-195 Causes Bronchopulmonary Dysplasia In Neonatal Mice, Patrick Philpot, Fred Graumuller, Nicole Melchiorre, Varsha Prahaladan, Xander Takada, Srinarmadha Chandran, Melissa Guillermo, David Dickler, Zubair H Aghai, Pragnya Das, Vineet Bhandari

Department of Pediatrics Faculty Papers

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O₂ (mild) and 60% O₂ (moderate) BPD. …

Functionalized Gold Nanoparticles And Halogen Bonding Interactions Involving Fentanyl And Fentanyl Derivatives, Molly M. Sherard, Jamie S. Kaplan, Jeffrey H. Simpson, Kevin W. Kittredge, Michael C. Leopold

Chemistry Faculty Publications

Fentanyl (FTN) and synthetic analogs of FTN continue to ravage populations across the globe, including in the United States where opioids are increasingly being used and abused and are causing a staggering and growing number of overdose deaths each year. This growing pandemic is worsened by the ease with which FTN can be derivatized into numerous derivatives. Understanding the chemical properties/behaviors of the FTN class of compounds is critical for developing effective chemical detection schemes using nanoparticles (NPs) to optimize important chemical interactions. Halogen bonding (XB) is an intermolecular interaction between a polarized halogen atom on a molecule and e−-rich …

Combined Use Of Donepezil And Memantine Increases The Probability Of Five-Year Survival Of Alzheimer’S Disease Patients, Ehsan Yaghmaei, Hongxia Lu, Louis Ehwerhemuepha, Jianwei Zheng, Sidy Danioko, Ahmad Rezaie, Seyed Ahmad Sajjadi, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.

Methods

We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. …

Poptosis Or Peptide-Induced Transmembrane Pore Formation: A Novel Way To Kill Cancer Cells Without Affecting Normal Cells, Matthew Pincus, Miriam Silberstein, Nitzan Zohar, Ehsan Sarafraz-Yazdi, Wilbur Bowne

Department of Surgery Faculty Papers

Recent advances in cancer treatment like personalized chemotherapy and immunotherapy are aimed at tumors that meet certain specifications. In this review, we describe a new approach to general cancer treatment, termed peptide-induced poptosis, in which specific peptides, e.g., PNC-27 and its shorter analogue, PNC-28, that contain the segment of the p53 transactivating 12-26 domain that bind to HDM-2 in its 1-109 domain, bind to HDM-2 in the membranes of cancer cells, resulting in transmembrane pore formation and the rapid extrusion of cancer cell contents, i.e., tumor cell necrosis. These peptides cause tumor cell necrosis of a wide variety of solid …

Increased Usage Of Doxycycline For Young Children With Lyme Disease, Amy Thompson, Desiree Neville, Laura Chapman, Fran Balamuth, Meagan Ladell, Anupam Kharbanda, Rachael Aresco, Lise Nigrovic

Department of Emergency Medicine Faculty Papers

Background: The 2018 Infectious Disease Committee of the American Academy of Pediatrics stated that up to 3 weeks or less of doxycycline is safe in children of all ages. Our goal was to examine trends in doxycycline treatment for children with Lyme disease.

Methods: We assembled a prospective cohort of children aged 1 to 21 years with Lyme disease who presented to one of eight participating Pedi Lyme Net centers between 2015 and 2023. We defined a Lyme disease case with an erythema migrans (EM) lesion or positive two-tier Lyme disease serology categorized by stage: early-localized (single EM lesion), early-disseminated …

Analysis Of Research And Development Trends Of New Drugs, Ping Xu, Li Xu, Ruo-Nan Yang, Wei Li, Kaixian Chen

Bulletin of Chinese Academy of Sciences (Chinese Version)

As an important component in the pharmaceutical innovation, research and development (R&D) of new drugs stands at the forefront of a new round of life science and technology revolution and bioeconomic reform, which is of strategic significance to leading scientific and technological innovation, driving economic development, and improving people’s health and well-being. At present, continuous innovation in cutting-edge technologies, cross-domain integration of disciplines, and digital depth enablement drive active innovation in the field of new drug R&D. Both domestically and internationally, innovative small molecule drugs, antibody drugs, immune cell therapy, gene therapy and nucleic acid drugs are receiving intensive market …

Proteomic Characterization And Cytotoxic Potential Of Proteins From Cuscuta (Cuscuta Epithymum (L.) Crude Herbal Product Against Mcf-7 Human Breast Cancer Cell Line, Umaima Akhtar, Yamna Khurshid, Bishoy El-Aarag, Basir Syed, Ishtiaq A. Khan, Keykavous Parang, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa.

Methods

The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun …

Exploring The Design Space Of Antifungal Peptides, Miryam Kikhwa

Seton Hall University Dissertations and Theses (ETDs)

The synthesis, characterization, and evaluation of antifungal activity of peptides FQ15 and FG10 will be conducted to address the hypothesis. The hypothesis of this thesis is that a peptide with similar properties to AS15 would have similar activity against Cryptococcus neoformans. This study addresses the challenge of drug- resistant microbes by developing inhibitors targeting lipid flippase and exploring their potential as antimicrobial agents against Cryptococcus neoformans. Chapter 1 provides a historical context of the background on the development of antimicrobials and common antifungal treatments, as well as an introduction about C. neoformans and its resistance mechanism. Chapter 2 introduces the …

Repurposing Clinically Relevant Metabolic Inhibitor Drugs, Difluoromethylornithine (Dfmo) And Orlistat, For Gammaherpesvirus Replication, Lay Paw

Honors Projects

Viruses, including herpesviruses, contribute up to 15% of all human cancers. Murine gammaherpesvirus-68 (MHV-68), a pathogen commonly found in mice, is studied due to its shared homology with several human herpesviruses. Studies done in the Delgado lab via metabolomics analysis show MHV-68 infected cells increase host cell metabolism. Clinically relevant metabolic inhibitor drugs, ɑ-Difluoromethylornithine (DFMO) and Orlistat, respectively block polyamine and lipid production demonstrated a reduction in MHV-68 viral production. Repurposing clinically relevant drugs through the exploration of a different target shows great promise in reducing oncogenic viral titer.

Fluorescence-Based Techniques For The Identification Of Small Biomolecules, Charnette Frederic

Seton Hall University Dissertations and Theses (ETDs)

Understanding fluorescence-based methods for detecting small biomolecules is a crucial area of focus in research investigations. Our studies focused on the challenge in two parts: Non-intrinsic fluorescence and intrinsic fluorescence. For studies on Non-intrinsic fluorescence, Rifampicin (Rif), an antibiotic harnessed for treating diverse bacterial infections, including tuberculosis (TB), serves as a focal point. Leveraging the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process, aptamers emerged from the nonspecific 40-mer Deoxyribonucleic Acid (DNA) library to interact with its target, Rif. During each SELEX cycle, the recovered nucleotides underwent amplification via Polymerase Chain Reaction (PCR) until the most selective aptamers were …

A Model Of Oocyte Population Dynamics For Fish Oogenesis, Louis Fostier, Frédérique Clément, Romain Yvinec, Violette Thermes

Biology and Medicine Through Mathematics Conference

No abstract provided.

Effects Of Drug Delivery On Ppi-Responsive Esophageal Eosinophilia, Alex Biller, Rachel Chevalier, Amornluck Krasaelap, Janelle R. Noel-Macdonnell

Research Days

Determine if formulation of proton pump inhibitory (pill/capsule vs liquid) affects eosinophilic infiltration of esophagus in patients with PPI-Responsive Esophageal Eosinophilia.

Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick

Kimmel Cancer Center Faculty Papers

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …