When's the last time we saw Isis looking at HCV? Been years. But Jason dug up a new and interesting paper that describes a ribosomal entry inhibitor:
Message 26436957
It turns out Isis got issued a patent in this area three months ago:
"Benzimidazoles and analogs thereof as antivirals"
patft.uspto.gov
Mind, this does not show up on the pipeline chart, even as a preclinical program. The research on it goes back to at least 2005, so they're not exactly putting a high priority on this . . .
>>J Med Chem. 2005 Nov 17;48(23):7099-102.
SAR by MS: discovery of a new class of RNA-binding small molecules for the hepatitis C virus: internal ribosome entry site IIA subdomain.
Seth PP, Miyaji A, Jefferson EA, Sannes-Lowery KA, Osgood SA, Propp SS, Ranken R, Massire C, Sampath R, Ecker DJ, Swayze EE, Griffey RH.
Ibis Therapeutics, A Division of Isis Pharmaceuticals Inc., 1891 Rutherford Road, Carlsbad, California 92008, USA.
A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub-micromolar affinity is reported. The benzimidazole 'hit' 1 with a KD approximately 100 microM to a 29-mer RNA model of Domain IIA was identified from a 180000-member library using mass spectrometry-based screening methods. Further MS-assisted SAR (structure-activity relationships) studies afforded benzimidazole derivatives with sub-micromolar binding affinity for the IIA RNA construct. The optimized benzimidazoles demonstrated activity in a cellular replicon assay at concentrations comparable to their KD for the RNA target.<<
Apparently they managed to keep this despite spinning Ibis out to Abbott. But they have a lot on their plate, and apparently are just indulging in resume padding at the moment. Maybe they've decided HCV is too crowded?
Cheers, Tuck |
