Innovation Pharmaceuticals Inc (IPIX)

[JSN2000]

Prurisol metabolism ... where does the MOA reside? We do know that abacavir is rapidly metabolized to inactive compounds " primarily through cytosolic alcohol dehydrogenase (ADH) and uridine diphosphate glucuronosyltransferase (UGT) enzymes" see https://www.pharmgkb.org/pathway/PA166104634. The primary active metabolite of abacavir in treating HIV is carbovir 5'-triphosphate. By adding glycolic acid to abacavir see http://www.google.com/patents/WO2013103601A1?cl=en ... prurisol is later hydrolyzed by esterases to glycolic acid and abacavir. The size of the carboxyl group apparently affects which carboxyl esterase (hCE1, hCE2) would predominate see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572478/ ... it would be interesting to see serum concentration data from the prurisol trials to gauge how it compares with abacavir (ZIAGEN). Glycolic acid is metabolized to oxalic acid. Oxalic acid is converted to oxalate. Understanding the pharmacodynamic interactions within the affected skin cells by these metabolites would help us know why the 2a results are showing some potential ... it will be interesting to see the phase 2b data.