Related Experiment Video
Updated: Sep 11, 2025

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
Published on: May 24, 2024
Valine-Niclosamide for Treatment of Androgen Receptor Splice Variant-Positive Hepatocellular Carcinoma
Emma J Hoelzen1, Hanna S Radomska1, Samuel K Kulp1
1Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Background/Objectives:
Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and currently is the second-leading cause of cancer-related mortality globally. Current front-line systemic therapies for advanced HCC offer only modest improvements in patient overall survival. HCC is a sexually dimorphic disease, and cancer progression is driven in part by AR activity. Here, we present novel niclosamide pro-drugs for use in advanced HCC based upon niclosamide's known anti-AR activity and additional anti-cancer pathway efficacy.
Methods:
Niclosamide analogs were evaluated for their impacts on the AR protein in two HCC cell lines with different AR phenotypes. Amino acid conjugates of niclosamide were developed, and pharmacokinetic (PK) analyses were conducted to determine improvements in clearance and oral exposure. Finally, niclosamide analogs and amino acid conjugates were evaluated in an in vivo model of HCC.
Results:
Niclosamide analogs maintained anti-AR properties in HCC. Valine-conjugated niclosamide showed improved oral exposure, positioning it as a potential therapeutic in advanced HCC.
Conclusions:
Valine-niclosamide improves upon niclosamide's poor solubility and oral bioavailability, increasing its utility for a variety of therapeutic uses. Further study of valine-niclosamide in advanced HCC and in other cancers or diseases is warranted.
More Related Videos
08:55Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
06:38An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Related Concept Videos
Treatment Resistant Cancers
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Drugs for Treatment of Ulcerative Colitis in IBD
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
Two synthetic agonists of THC,...