Emprumapimod

Emprumapimod is a potent, orally bioavailable and selective inhibitor of p38α MAPK directly inhibits LPS-induced IL-6 production from RPMI-8226 cell (IC50=100 pM). Emprumapimod can be used for the research of dilated cardiomyopathy and acute inflammatory pain[1][2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> MAPK/ERK Pathway >> p38 MAPK

Research Areas >> Inflammation/Immunology

p38α:100 pM (IC50)

In SCID-beige mice, LPS (3 μg/kg) induced IL-6 (7897±827 pg/mL) and TNF-α (1922±282 pg/mL) after 2 hours and these cytokines are inhibited by oral administration of Emprumapimod (ARRY-797; 30 mg/kg) by 91% and 95%, respectively[1]. In MM xenograft models, Emprumapimod (30 mg/kg, BID, PO) inhibits RPMI 8226 tumor growth by 72% as a single agent and by 56% when LPS is administered to stimulate growth in vivo[1]. Emprumapimod also inhibits LPS-induced phosphorylation of p38 in RPMI-8226 xenografts[1]. Treatment of LmnaH222P/H222P mice with the p38α inhibitor Emprumapimod (ARRY-371797; 30 mg/kg; orally twice daily; for 4 weeks initiated at 16 weeks of age) prevents left ventricular (LV) dilatation and deterioration of fractional shortening (FS). LV end-diastolic diameter (LVEDD) and LV end-systolic diameter (LVESD) in LmnaH222P/H222P mice treated with Emprumapimod are significantly smaller and FS is significantly increased compared with the placebo-treated mice[2]. Animal Model: LmnaH222P/H222P mice were[2] Dosage: 30 mg/kg Administration: Administered orally by gavage starting when mice were 16 weeks of age and continuing until 20 weeks of age Result: There were significant increases in LVEDD and LVESD as well as a decrease in FS, a parameter directly proportional to the LV ejection fraction.

[1]. Dale Wright, et al. ARRY-797, a Potent and Selective Inhibitor of p38 Map Kinase, Inhibits LPS-Induced IL-6 and In Vivo Growth of RPMI-8226 Human Multiple Myeloma Cells.

[2]. Antoine Muchir, et al. Abnormal p38α mitogen-activated protein kinase signaling in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2012 Oct 1;21(19):4325-33.