ETX0282 is an oral prodrug of a class A, C, and D serine β-lactamase inhibitor in clinical development for drug-resistant enterobacterial infections in combination with the beta-lactam drug cefpodoxime proxetil. Impressively ETX0282 had no observed adverse effect levels (NOAELs) of 500 mg/kg/day and 400 mg/kg/day in rat and dog, respectively, [...]

MK-5204 is a broad spectrum Candida antifungal agent derived from the natural product, enfumafungin. I was impressed that the molecule not only demonstrates oral efficacy but also has good oral PK in higher species (dog, cyno), given that the molecule is a large zwitterion with several very polar groups, including a primary amide, primary [...]

AL-611 is a prodrug to a nucleoside inhibitor of HCV NS5B polymerase. While there have been very successful nucleoside drugs (e.g. sofosbuvir), several nucleoside inhibitors of HCV previously failed in the clinic due to severe toxicities, in some cases due to incorporation of the nucleosides into host RNA. The Janssen Biopharma (formerly [...]

QPX7728 is an ultrabroad-spectrum beta-lactamase inhibitor with activity against both serine and zinc metallo-beta-lactamases, in contrast to approved beta-lactamase inhibitors such as relebactam which are only active against serine metalloproteases. Interestingly, the boron of the molecule coordinates to serine hydroxyl groups in serine [...]

“compound 9” is an investigational prodrug of pibrentasvir (ABT-530), a key component of AbbVie’s marketed HCV combination Mavyret. Pibrentasvir (PIB) is the largest approved oral small molecule since 1983 (MW = 1113, not including the peptide semaglutide at MW = 4113), and came with some solubility issues (aq. sol. pH 7 = <0.0001 mg/mL). The [...]