Medicinal polypharmacology is one answer to the complex reality of multifactorial human diseases that are often unresponsive to single-targeted treatment. It is an admittance that intrinsic feedback mechanisms, crosstalk, and disease networks necessitate drugs with broad modes-of-action and multitarget affinities. Medicinal polypharmacology grew to be an independent research field within the last two decades and stretches from basic drug development to clinical research. It has developed its own terminology embedded in general terms of pharmaceutical drug discovery and development at the intersection of medicinal chemistry, chemical biology, and clinical pharmacology. A clear and precise language of critical terms and a thorough understanding of underlying concepts is imperative; however, no comprehensive work exists to this date that could support researchers in this and adjacent research fields. In order to explore novel options, establish interdisciplinary collaborations, and generate high-quality research outputs, the present work provides a first-in-field glossary to clarify the numerous terms that have originated from various individual disciplines.
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http://dx.doi.org/10.3389/fphar.2024.1419110 | DOI Listing |
Eur J Med Chem
December 2024
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N. Pine St., Baltimore, MD, 21201, USA; University of Maryland Marlene & Stewart Greenebaum Comprehensive Cancer Center, 22 S. Greene St., Baltimore, MD, 21201, USA. Electronic address:
Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
National Center for Natural Products Research, University of Mississippi, University, Mississippi 38677, United States.
Cannabinoid receptor 1 (CB1R) has been extensively studied as a potential therapeutic target for various conditions, including pain management, obesity, emesis, and metabolic syndrome. Unlike orthosteric agonists such as Δ-tetrahydrocannabinol (THC), cannabidiol (CBD) has been identified as a negative allosteric modulator (NAM) of CB1R, among its other pharmacological targets. Previous computational and structural studies have proposed various binding sites for CB1R NAMs.
View Article and Find Full Text PDFPharm Res
January 2025
Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA.
Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C 1x), decursinol angelate (DA, C ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C ~ 1000x).
View Article and Find Full Text PDFBioact Mater
March 2025
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China.
Despite significant advances in targeted therapies and immunotherapies, non-small cell lung cancer (NSCLC) continues to present a global health challenge, with a modest five-year survival rate of 28 %, largely due to the emergence of treatment-resistant and metastatic tumors. In response, we synthesized a novel bioactive compound, ethyl 6-chlorocoumarin-3-carboxylyl L-theanine (TClC), which significantly inhibited NSCLC growth, epithelial mesenchymal transition (EMT), migration, and invasion and tumor growth and metastasis without inducing toxicity. TClC disrupts autocrine loops that promote tumor progression, particularly in stem-like CD133-positive NSCLC (CD133+ LC) cells, which are pivotal in tumor metastasis.
View Article and Find Full Text PDFACS Omega
December 2024
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, United States.
Despite promising preliminary biology, natural products isolation efforts may be confounded when the active compound is not isolated during bioassay-guided purification or classical pharmacognostic research investigations. A more rational isolation procedure connecting the polypharmacology of an herb to its individual constituents must be applied to better detect bioactive molecules before tedious analytical steps are considered. While (yohimbe) has been traditionally used in herbal medicine as a general tonic, an aphrodisiac, a performance enhancer, and an integral part of various dietary supplements, the hydroethanolic extract of yohimbe was identified to possess at least 3-4-fold induction of the pregnane X receptor (PXR) at 30 μg/mL, a key nuclear receptor implicated in adverse interactions, .
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