Pharmaceutics and Drug Design Commons^™

Tramadol For Treatment Of Neurogenic Cough: A Retrospective Case Series, Benjamin Joseph Rubinstein, Sheela Saidha, John Todd Sinacori

Department of Otolaryngology (ENT) Faculty Publications

Objectives

Explore the efficacy of tramadol for neurogenic cough and describe the longitudinal treatment experience.

Methods

A retrospective case series of adults with chronic cough who were treated with tramadol for neurogenic cough. A complete response was defined as no pathologic coughing, and a partial response was defined as 50% or greater reduction in severity or frequency.

Results

Sixty-nine patients were included. 38% of patients reported a complete response with an additional 33% reporting a partial response. The most common successful dosing regimen was 50 mg BID. Age, gender, and BMI did not impact treatment response. Patients with a history …

Self-Assembly Of Anti-Inflammatory Peptide Amphiphiles For Mucosal Health, Maria José Gómara, Ignacio Pérez-Pomeda, Ramon Pons, Paul Ziprin, Carolina Herrera, Isabel Haro

CONRAD Publications

Broad spectrum anti-inflammatory peptide amphiphiles (AIF-PAs) have been developed as an innovative strategy for the treatment of chronic mucosal inflammation and the prevention of HIV transmission. Novel lipopeptides based on two linear sequences of anti-inflammatory peptides were obtained by solid-phase peptide chemistry. In a pilot study, ex vivo exposure of colorectal tissue explants from Crohn's disease patients to AIF-PAs induced a downregulation of the proinflammatory profile. Furthermore, the HIV inhibitory potency of AIF-PAs was evaluated ex vivo in colorectal tissue explants, obtaining sub-micromolar IC₅₀ values. Characterization of AIF-PAs self-aggregation in aqueous solution revealed that the net charge distribution within the …

Off-Label Uses Of Deucravacitinib For Inflammatory Skin Conditions: Cases And Literature Review, Alexandra Nigro, Isabel C. Silva, Benjamin Gerstein, Jasper Dayanan, Saakshi Khattri

Department Dermatology Faculty Publications

Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Deucravacitinib may offer a more selective approach compared to traditional Janus kinase (JAK) inhibitors. Emerging data support the use of deucravacitinib in inflammatory dermatoses beyond psoriatic disease. We present our clinical experience using deucravacitinib off-label in patients with challenging inflammatory skin disease and contextualize our findings within the current literature. We report three female patients aged 31–63 years with refractory inflammatory skin conditions, including two with dermatomyositis and one with pityriasis rubra pilaris (PRP). All patients had persistent …

Depemokimab: A Twice Yearly Anti-Il 5 Biologic For Chronic Rhinosinusitis With Nasal Polyps (Crswnp) - A Narrative Review, Marn Joon Park, Joseph K. Han, Kent K. Lam

Department of Otolaryngology (ENT) Faculty Publications

Depemokimab is a monoclonal antibody that targets interleukin-5 with enhanced binding affinity and an extended terminal elimination half‑life of 6-8 weeks. The unique pharmacodynamic features of depemokimab enable sustained suppression of type 2 inflammation with twice‑yearly subcutaneous dosing. This narrative review provides details of depemokimab's molecular profile, pharmacokinetics, and pharmacodynamics and results regarding the clinical efficacy and safety of depemokimab from recently published Phase 3 clinical trials for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). In 528 severe adult CRSwNP patients (ANCHOR‑1/‑2 trials), depemokimab achieved Δ total endoscopic nasal polyp score by -0.70 (p <  .001) and Δ nasal obstruction verbal response scale by -0.24 (p = .003) at week 52, compared to placebo. Twice‑yearly 100 mg depemokimab provides durable eosinophil suppression and with a safety profile comparable to placebo in Phase 3 trials for CRSwNP. Future work should refine biomarkers and assess comparative cost‑effectiveness and long‑term adherence, safety, and effectiveness.

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani

Department of Medicine Faculty Publications

[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good …

Longitudinal Patterns Of Urinary Biomarkers Of Placental And Renal Function In Pregnancy And Associations With Early Pregnancy Exposure To Phthalates And Replacements, Erin E. Mcnell, Danielle R. Stevens, Barrett M. Welch, Suzanne Fenton, Antonia M. Calafat, Julianne Cook Botelho, Elena Sinkovskaya, Ann Przybylska, George Saade, Alfred Abuhamad, Kelly K. Ferguson

Department of Obstetrics & Gynecology Faculty Publications

Phthalates and replacements are endocrine-disrupting chemicals that may interfere with early pregnancy processes such as placentation and renal adaptation. Placental and renal biomarkers may help examine these toxicologic mechanisms. This study aims to characterize longitudinal changes in urinary protein biomarkers of placental angiogenesis (sFlt-1, PlGF, sEng) and renal function (KIM-1, NGAL, nephrin), and investigate associations with early pregnancy exposure to phthalates and replacements. Among 291 participants from the Human Placenta and Phthalates prospective cohort, urinary metabolites of eight phthalates and two replacements were quantified at up to 2 time points from 12 to 15 weeks gestation. Repeated measures were averaged …

Sglt2 Inhibitors In Cardio-Oncology: A Systematic Review And Meta-Analysis, Luigi Spadafora, Marco Bernardi, Gianmarco Sarto, Beatrice Simeone, Erica Rocco, Salvatore Carbone, Laura Adelaide Dalla Vecchia, Roberto Franco Enrico Pedretti, Valentina Valentine, Rachele Di Mario, Maurizio Forte, Giacomo Frati, Antonio Abbate, Michele Golino, Francesco Versaci, Mariangela Peruzzi, Pierre Sabouret, Giuseppe Biondi Zoccai, Sebastiano Sciarretta

EVMS School of Health Professions Faculty Publications

Background

According to available evidence, sodium-glucose cotransporter-2 inhibitors (SGLT2i) may confer cardioprotection in patients with cancer undergoing chemotherapy.

Objectives

The objective of the study was to evaluate the impact of SGLT2i on all-cause mortality and heart failure (HF) outcomes in this population.

Methods

We searched PubMed, Cochrane CENTRAL, and Embase through August 2025 for studies of SGLT2i in adult patients with cancer. Random-effects models were used to pool effects for all-cause mortality and an HF composite (new-onset HF and/or HF hospitalization) in cancer patients >18 years. Meta-regression tested effect modification by beta-blockers, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, age, and …

Synthesis And Evaluation Of Anti-Hiv Activity Of Fatty Acyl Conjugates Of Tenofovir Alefanamide, Muhammad Sajid, Naglaa Salem El-Sayed, Louise A. Ouattara, Amita Verma, Gustavo F. Doncel, Keykavous Parang, M. Iqbal Choudhary, Hina Siddiqui

CONRAD Publications

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by intracellular enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent this limitation, several prodrug approaches have been proposed and developed. Herein, we hypothesized that the conjugation of anti-HIV fatty acids with the nucleotide tenofovir alafenamide (TAF) (1) could improve the anti-HIV activity of the nucleotide. Several fatty acyl amide conjugates of TAF were synthesized and evaluated in comparative studies with TAF. The synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single-round HIV-1 infection assay …

Scaffolds With Spatiotemporally Controlled Growth Factor Delivery And Cyclodextrin-Enabled Antagonism Of Growth Factor Receptor Sequestration Promote Cutaneous Wound Healing, Jelena Marjanovic, Veronica Jurczuk, Lilian Valadares Tose, Yarixa Cintron Diaz, Francisco Fernandez Lima, Beatriz Abdo Abujamra, Sara Danker, Sinan Jabori, Devinder Singh, Jamie L. Burgess, Joshua Tam, Mohamadmahdi Samandari, Rivka C. Stone, Stephen C. Davis, Robert S. Kirsner, Marjana Tomic-Canic, Fotis M. Andreopoulos, Ivan Jozic

Mechanical & Aerospace Engineering Faculty Publications

Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach …

Gramseq-Dta: A Grammar-Based Drug-Target Affinity Prediction Approach Fusing Gene Expression Information, Kasul Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Drug–target affinity (DTA) prediction is a critical aspect of drug discovery. The meaningful representation of drugs and targets is crucial for accurate prediction. Using 1D string-based representations for drugs and targets is a common approach that has demonstrated good results in drug–target affinity prediction. However, these approach lacks information on the relative position of the atoms and bonds. To address this limitation, graph-based representations have been used to some extent. However, solely considering the structural aspect of drugs and targets may be insufficient for accurate DTA prediction. Integrating the functional aspect of these drugs at the genetic level can enhance …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

The Short And Sweet On Sodium-Glucose Cotransporter Inhibitors And Glucagon-Like Peptide-1 Receptor Agonists In Heart Failure, Jose L. Batista, Tracy Makuvire, Jonathan D. Davis, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Heart failure (HF) affects 6 million people in the US, and type 2 diabetes (T2D) is a significant risk factor for HF. Since 2008, regulatory agencies have required cardiovascular safety trials for new T2D therapies, and these have consistently demonstrated the cardiovascular benefits of glucose-lowering drugs. Sodium-glucose cotransporter inhibitors (SGLTi) and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs)/glucose-dependent insulinotropic polypeptide (GIP) reduce major adverse cardiovascular events and deaths, regardless of diabetes status, and improve cardiorespiratory fitness. SGLTis, such as dapagliflozin and empagliflozin, benefit patients with reduced and preserved ejection fraction, significantly reducing HF hospitalizations and cardiovascular deaths. The DAPA-HF and EMPEROR-Reduced …

Association Of Prenatal Exposure To Phthalates And Phenols With Adverse Pregnancy Outcomes, Misa Hayasaka, Diana Aboukhater, George Saade, Tetsuya Kawakita

Department of Obstetrics & Gynecology Faculty Publications

OBJECTIVE:

To evaluate the association between prenatal exposures to phthalates and phenols and adverse pregnancy outcomes, including preterm birth (PTB), small-for-gestational-age (SGA) birth weight, and gestational diabetes mellitus (GDM).

METHODS:

This study analyzed data from the Environmental Influences on Child Health Outcomes consortium, which harmonized longitudinal data on more than 30,000 pregnancies and 57,000 children from 69 cohorts across the United States and Puerto Rico. Pregnancy outcomes included PTB, SGA, and GDM, identified from medical records or self-reports. Generalized estimating equations models with Poisson distribution and robust variance were used to estimate relative risks (RRs) and 95% CIs per interquartile …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

Targeting Bone In Cancer Therapy: Advances And Challenges Of Bisphosphonate-Based Drug Delivery Systems, Fariba Ganji, Mohammadmahdi Eshaghi, Hossein Shaki, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Background and Purpose: Bisphosphonates (BPs) are well-known for their strong affinity toward bone mineral matrices and are widely used to inhibit excessive osteoclast activity associated with various bone disorders. Beyond their clinical use, their unique bone-targeting capability has positioned them as promising ligands for drug delivery systems aimed at treating bone-related cancers. Approach: The review analyses published studies on BP-functionalized drug delivery systems, including direct drug conjugates, calcium-based nanomaterials, carbon-based nanostructures, and self-assembling systems such as micelles and liposomes. In vitro assays (e.g. hydroxyapatite binding, cell viability) and in vivo biodistribution studies are discussed to evaluate targeting efficiency and …

Novel Micro-And Nanoformulations Of Paclitaxel For Targeting Metastatic Breast, Non-Small Cell Lung, And Pancreatic Cancers, Lobat Tayebi, Mehran Alavi

Electrical & Computer Engineering Faculty Publications

Nonlinear pharmacokinetics resulting from high lipophilic and low oral bioavailability, and hypersensitivity reactions and hyperlipidemia caused by formulation by Cremophor EL have limited clinical effectiveness of paclitaxel (Taxol). In this way, there is the critical necessity of innovative drug delivery systems (DDSs) to mitigate severe side effects and overcome clinical limitations of paclitaxel. In recent years, various micro- and nanoformulations, specifically polymeric nanoparticles (NPs) and lipid NPs, have been presented and approved by the Food and Drug Administration (FDA). In addition, other nanoformulations, such as polymeric nanoparticles (NPs), micelles, liposomes, and mesoporous silica nanoparticles, have shown promising results in vitro …

Magnetic And Ph-Sensitive Dual Actuation Of Biohybrid Microswimmer Of Targeted Drug Release Suitable For Cancer Cell Microenvironment, Richa Chaturvedi, Yumin Kang, Yunji Eom, Sri Ramulu Torati, Cheolgi Kim

Center for Bioelectronics Publications

The chemotherapeutic agents most frequently used in cancer treatment often have limited effectiveness because of their low specificity for tumors and poor therapeutic performance. In addition to the aforementioned therapeutic challenges the drug delivery carriers conjugated with the drug encounter early detection and elimination from the immune system before arriving at the affected area continues to be a significant research focus among researchers. To address this prevalent issue, an effective approach has been developed that leverages the physiological differences between normal and tumor tissue to enhance the efficacy of anticancer drugs. This drug delivery system is designed based on pH-sensitive …

A Semiparametric Modeling Approach For Analyzing Clinical Biomarkers Restricted To Limits Of Detection, Sandipan Dutta, Susan Halabi

Mathematics & Statistics Faculty Publications

Before biomarkers can be used in clinical trials or patients' management, the laboratory assays that measure their levels have to go through development and analytical validation. One of the most critical performance metrics for validation of any assay is related to the minimum amount of values that can be detected and any value below this limit is referred to as below the limit of detection (LOD). Most of the existing approaches that model such biomarkers, restricted by LOD, are parametric in nature. These parametric models, however, heavily depend on the distributional assumptions, and can result in loss of precision under …

De Novo Prediction Of Drug–Target Interactions Using Laplacian Regularized Schatten P-Norm Minimization, Gaoyan Wu, Mengyun Yang, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

In pharmaceutical sciences, a crucial step of the drug discovery is the identification of drug–target interactions (DTIs). However, only a small portion of the DTIs have been experimentally validated. Moreover, it is an extremely laborious, expensive, and time-consuming procedure to capture new interactions between drugs and targets through traditional biochemical experiments. Therefore, designing computational methods for predicting potential interactions to guide the experimental verification is of practical significance, especially for de novo situation. In this article, we propose a new algorithm, namely Laplacian regularized Schatten p-norm minimization (LRSpNM), to predict potential target proteins for novel drugs and potential drugs for …

Drug Repositioning Based On Bounded Nuclear Norm Regularization, Mengyun Yang, Huimin Lao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Computational drug repositioning is a cost-effective strategy to identify novel indications for existing drugs. Drug repositioning is often modeled as a recommendation system problem. Taking advantage of the known drug–disease associations, the objective of the recommendation system is to identify new treatments by filling out the unknown entries in the drug–disease association matrix, which is known as matrix completion. Underpinned by the fact that common molecular pathways contribute to many different diseases, the recommendation system assumes that the underlying latent factors determining drug–disease associations are highly correlated. In other words, the drug–disease matrix to be completed is low-rank. Accordingly, …

Wake Me When It's Over- Bacterial Toxin-Antitoxin Proteins And Induced Dormancy, Nathan P. Coussens, Dayle A. Daines

Biological Sciences Faculty Publications

Toxin-antitoxin systems are encoded by bacteria and archaea to enable an immediate response to environmental stresses, including antibiotics and the host immune response. During normal conditions, the antitoxin components prevent toxins from interfering with metabolism and arresting growth; however, toxin activation enables microbes to remain dormant through unfavorable conditions that might continue over millions of years. Intense investigations have revealed a multitude of mechanisms for both regulation and activation of toxin-antitoxin systems, which are abundant in pathogenic microorganisms. This minireview provides an overview of the current knowledge regarding type II toxin-antitoxin systems along with their clinical and environmental implications.