Human iPSC-derived Cardiomyocytes and Pyridyl-Phenyl Mexiletine Analogs
In the United States, almost one million individuals are hospitalized every year for cardiac arrhythmias, making arrhythmias one of the top causes of healthcare expenditures with a direct cost of almost $50 billion annually. Almost 300,000 individuals die of sudden arrhythmic death syndrome every year.
Ventricular cardiac arrhythmia arises in acquired or congenital heart disease. Arrhythmias are very common in older adults but unfortunately, drugs to treat arrhythmias have liabilities. In addition, numerous investigational drugs have been withdrawn from the market because they induce QT prolongation and a potentially fatal ventricular tachycardia, a condition called Torsade de Pointes. For normal heart cell function, sodium channels rapidly inactivate with depolarization. In depolarization of cardiomyocytes, sodium channels open briefly and allow influx of sodium. Correct regulation of ion currents in cardiomyocytes is key for proper heart function.
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https://www.sciencedirect.com/science/article/abs/pii/S0960894X21003899?via%3Dihub
Anti-Arrhythmic Hit to Lead Refinement in a Dish using Patient-Derived iPSCs
In the United States, almost one million individuals are hospitalized every year for cardiac arrhythmias, making arrhythmias one of the top causes of healthcare expenditures with a direct cost of almost $50 billion annually. Almost 300,000 individuals die of sudden arrhythmic death syndrome every year.
Medicinal chemists at the Human BioMolecular Research Institute (HBRI), in San Diego, CA, and stem cell biologists at Stanford University, in Stanford, CA, and cardiovascular pharmacologists at UCLA in Los Angeles, CA and Columbia University, in New York City, NY, respectively, reported on reengineered mexiletine compounds that showed improved potency and decreased toxicity in addressing ventricular cardiac arrhythmia.
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https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.0c01545
The Conrad Prebys Foundation funds the Human BioMolecular Research Institute to research a drug candidate to fight drug-resistant pancreatic cancer!
San Diego, Calif., March 23, 2021 – A collaborative team at the Human BioMolecular Research Institute (HBRI) will utilize The Conrad Prebys Foundation award to develop a drug candidate that potently inhibits drug resistant human pancreatic cancer stem cells and inhibits metastasis and relapse via a novel mechanism. HBRI has already identified a drug candidate that shows efficacy to eradicate pancreatic cancer stem cells and HBRI scientists are eager to develop the candidate in partnership with The Conrad Prebys Foundation.
“Pancreatic cancer drug-sensitivity predicted by synergy of PAWI-2 and protein biomarker expression”
Potent inhibitor of pancreatic cancer stem cells that synergizes current standard of care, PAWI-2 is featured in Investigational New Drugs.
San Diego, Calif., September 16, 2020 – Researchers at the Human BioMolecular Research Institute and ChemRegen, Inc., reported that a small molecule potently inhibited pancreatic cancer stem cells and also synergized standard of care drugs. Publishing September 15, 2020, in the journal Investigational New Drugs, the team describes how they tested PAWI-2, a man-made, drug-like chemical that can be used to inhibit pancreatic cancer stem cells and other cancer. The researchers discovered PAWI-2 acted as a synergist to make heretofore poorly potent drugs that previously did not show much efficacy in humans work much better in in vitro studies.
