Thursday, April 9, 2015

Derek Lowe Has A Very Interesting Story -- On A "Way-Retro" Candidate Showing Hep C Efficacy -- In Animal Models

Do go read all of his at -- In The Pipeline blog.

The image at right is the throwback's structure, an old (ancient!) antihistamine. . . truly a Neanderthal among such drugs.


. . . .A new report suggests that an existing antihistamine, chlorcyclizine (CCZ), could be an effective therapy. Check out that structure - that's a first-generation antihistamine if you ever saw one (the old fuzzy-headed allergy season effect). It's been over-the-counter for dog's years. . . . 

But this new paper, from NIH and a collaborator at Hiroshima University, makes a good case for it as an antiviral. A cell-based phenotypic assay identified it in a screen of approved drugs, and several related compounds hit as well. Both enantiomers of CCZ seemed to work, so they chose the (S), since it had less histamine receptor activity. It dose-responsed well in assays measuring viral RNA levels in infected cells, and the activity seems to cross all the viral genotypes tested, without any noticeably cytotoxicity. Follow-up assays showed that viral RNA replication doesn't seem to be the target, nor virion assembly. It's back earlier than those, and the best hypothesis now is that it's a cell entry inhibitor. But none of the proteins known to be factors in HCV cell entry appear to be affected, so the target hunt is still very much on. . . .

And do be kind -- to one another.

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