Rational drug design company ImmunoPharmaceutics Inc. (IPI)announced today that it has filed an application with the U.S.Patent and Trademark Office for its lead compound IPI 413, anendothelin receptor subtype A antagonist, as well as a numberof "backup" subtype A compounds with which it intends toinitiate preclinical and clinical development activities.
The compound IPI 413 is a low molecular weight non-peptide;it binds to the desired subtype A receptors at nanomolarconcentrations.
Endothelin, a small protein discovered about four years ago,turns out to be the most potent naturally occurringvasoconstrictor known. It's been shown to play a role in anumber of disease processes, including hypertension,myocardial infarction and acute renal failure. Most of thesedata come from animal models, but there is somecircumstantial evidence of endothelin's effects on hypertensionin humans.
"There have been a number of studies in kidney dialysispatients indicating that, upon the administration oferythropoietin, the patients get elevated levels of endothelin,which are associated with a state of hypertension," said EdwardMaggio, president and chief executive officer of IPI.
There are a number of endothelin precursors (it's processedfrom a pre-pro-drug form) as well as several receptorsubtypes. The subtype A receptor is largely associated withcardiovascular and renal disease, and is of the most interestcurrently in the pharmaceutical field, Maggio told BioWorld.Receptor subtype B, whose potential clinical utility has notbeen as well demonstrated in animal models, is found inbronchial passages and thus could be associated withbronchocontractive and pulmonary disorders, Maggioexplained.
IPI scientists have constructed their receptor antagonists viasecond-generation rational drug design technology. They startwith a pharmacologically active peptide, extract the three-dimensional structural coordinates of the pharmacophore, anduse that information to create low molecular weight non-peptide drugs.
IPI used this technology to come up with its lead receptorsubtype A antagonist, IPI 413, as well as a series of closelyrelated compounds. "This represents the first systematicconversion of a pharmacologically active peptide into a non-peptide small molecule," Maggio told BioWorld.
The company has also used the method to define thecoordinates of the endothelin receptor subtype Bpharmacophore and has succeeded in generating one or moreendothelin subtype B specific antagonists that have nanomolaractivity.
IPI, formed in 1989 as a subsidiary of Synbiotics Corp., raised$2.8 million in equity financing in June 1991. The companyraised about $1.25 million in a placement of series B stock toone of its original investors and to Japan American Finance Co.(JAFCO) in May 1992, Maggio said.
IPI is currently in the midst of completing another privateplacement. The company is also seeking R&D partners todevelop its receptor subtype A antagonists, and also intends toseek collaborators for the subtype B antagonists in the future,Maggio said.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.