Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation. PMF disrupts the physiologic medullary erythropoietic environment and causes anemia symptoms. The JAK-STAT pathway plays a role in MF pathogenesis. Momelotinib is an orally active JAK1/JAK2 kinases inhibitor with IC50 values of 26.9 nM and 1.4 nM for JAK1 and JAK2, respectively. Hence, we introduce Momelotinib, the FDA approved drug that suppresses hepcidin expression by inhibiting IL-6/JAK/ATAT3, leading to restoration of iron homeostasis and therefore benefit on iron-restricted anemia.
Momelotinib can become a promising new therapy strategy for Atopic dermatitis (AD)
In vivo, Momelotinib improved the symptoms of AD histologically reduced the skin severity scores and total serum IgE levels in hapten-induced AD model mice. Momelotinib down-regulated the mRNA expression of IL-4, IL-5, IFN-γ and TSLP, and inhibited the phosphorylation of STAT1, STAT3 and STAT5 in skin lesions.
In vivto, Momelotinib reduced the expression of CD80, CD86, MHCII and mRNA of OX40L in TSLP-activated dendritic cells.
In summary, Momelotinib is an orally active JAK1/JAK2 inhibitor suppressing the signal transduction of multiple pro-inflammatory cytokines and restorating of iron homeostasis.
Reference:
[1] J Hematol Oncol. 2022 Jan 19;15(1):7.
[2] Int J Mol Sci. 2018 Dec 10;19(12):3973.