MPL-5821 / Macrophage Pharma - LARVOL DELTA

Targeted p38 mitogen-activated protein kinase inhibition potently augment inflammatory responses of human macrophages toward Staphylococcus aureus. (PubMed, Mol Immunol) - "Since systemic p38α kinase inhibition cause aberrant toxicity, we used the myeloid specific p38α kinase inhibitor, MPL-5821...Our study thus unravels a novel and specific activation of macrophages that augment their response toward S. aureus, without causing aberrant inflammation. This constitutes a unique non-antibiotic therapeutic approach that can potentially be used against persistent S. aureus infection."

Journal • Infectious Disease • Inflammation • CXCL8 • IFNG • IL1B • IL6 • TNFA

MPL-5821, a macrophage targeted ESMTM p38 MAPK inhibitor, inhibits the production of TLR agonist induced IL-10 whilst sparing T-cell functionality (AACR 2018) - "...MPL-5821 is an ESMTM p38 MAPK inhibitor which not only inhibits IL-10 but also enhances LPS stimulated IL-12p70 and in contrast to conventional p38 MAPK inhibitors provides enhancement of lymphocyte IFN production.The present studies contrast MPL-5821 with multiple non-targeted agents, including inhibitors of HDAC, JAK, PI3K, MEK and CSF-1R, in human PBMC assays...MPL-5821 potently inhibited the R848 induced IL-10 production as measured by Cytometric Bead Array and in contrast to a conventional p38 MAP inhibitor LY2228820 also enhanced IFN production.We studied MPL-5821 in cell suspensions prepared from human ovarian tumor and ascites...MPL-5821 again showed potent inhibition of TLR agonist induced IL-10 with concomitant enhancement of IFN production. We conclude that application of ESMTM technology to macrophage selective delivery of p38 MAPK inhibitors has the potential to inhibit TLR agonist induction of IL-10, which is implicated in limiting the performance of TLR agonist

Cervical Cancer • Ovarian Cancer