naldemedine

Naldemedine (S 297995) is a peripheral selective μ-opioid receptor antagonist being developed by Shionogi for the treatment of opioid-induced adverse reactions, including constipation, nausea, and vomiting. They are usually well tolerated, mainly with mil

Naldemedine tosylate (S-297995) is an orally active μ-opioid receptor antagonist (PAMORA) with high binding affinities (K_i = 0.34, 0.43, 0.94 nM) and potent antagonist activities (IC_50 = 25.57, 7.09, 16.1 nM) towards human recombinant μ-, δ-, and κ-opioid receptors, respectively. It is utilized in research on opioid-induced constipation (OIC) and is anticipated to interact with the 3CL proenzyme encoded by the SARS-CoV-2 genome.

CB-1158-analog, also known as Numidargistat-analog and INCB01158-analog, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).