SA91-0178 is a METTL1 inhibitor. SA91-0178 inhibits m 7 G methylation of RNA, reduces SARM1 stability, mitigates NAD + depletion and metabolic reprogramming in macrophages. SA91-0178 demonstrates excellent protective efficacy against multiple organ injury in cecal ligation and puncture (CLP)-induced and ischemia/reperfusion (I/R)-induced mice. SA91-0178 can be used for the study of systemic inflammatory diseases [1].
In Vivo, SA91-0178 (5-15 mg/kg, ip, once) demonstrates protective effects against multiple organ injury in cecal ligation and puncture (CLP)-induced septic C57BL/6 mice, while failing in Lyz2creMettl1fl/fl mice[1].
In Vitro, SA91-0178 inhibits LPS -induced TNF-α and IL-1β secretion in mouse bone marrow-derived macrophages (BMDMs) without cytotoxicity[1]. SA91-0178 attenuates LPS-induced m7G modification in RAW264.7 cells and human peripheral blood mononuclear cell (PBMC)-derived macrophages[1]. SA91-0178 reduces luciferase activity of wild-type SARM1 3'UTR reporter in shMETTL1-treated THP-1-derived macrophages[1].
References:
[1]. Hou C, et al. METTL1-mediated m7G methylation of Sarm1 mRNA promotes macrophage inflammatory responses and multiple organ injury. Sci Immunol. 2025 Sep 5;10(111):eadv4810.
In Vivo, SA91-0178 (5-15 mg/kg, ip, once) demonstrates protective effects against multiple organ injury in cecal ligation and puncture (CLP)-induced septic C57BL/6 mice, while failing in Lyz2creMettl1fl/fl mice[1].
In Vitro, SA91-0178 inhibits LPS -induced TNF-α and IL-1β secretion in mouse bone marrow-derived macrophages (BMDMs) without cytotoxicity[1]. SA91-0178 attenuates LPS-induced m7G modification in RAW264.7 cells and human peripheral blood mononuclear cell (PBMC)-derived macrophages[1]. SA91-0178 reduces luciferase activity of wild-type SARM1 3'UTR reporter in shMETTL1-treated THP-1-derived macrophages[1].
References:
[1]. Hou C, et al. METTL1-mediated m7G methylation of Sarm1 mRNA promotes macrophage inflammatory responses and multiple organ injury. Sci Immunol. 2025 Sep 5;10(111):eadv4810.