IM-12 (GMP)

IM-12 GMP is an orally effective anti-inflammatory agent that targets and inhibits the NF-κB and STAT3 signaling pathways. IM-12 GMP activates the Wnt signaling pathway and promotes the nuclear translocation of β-catenin by inhibiting GSK3β, while also blocking the tyrosine kinase activity of p210BCR/ABL. IM-12 GMP reduces the levels of IL-6, IL-17, NO, prostaglandin E2, iNOS and COX-2, and induces ER stress, Ca²⁺ release, autophagy and apoptosis. IM-12 GMP is heat-sensitive and does not induce autophagy in IM-resistant p210BCR/ABL^T315I mutant cells. IM-12 GMP is also a component of the 5iLA medium used for naive pluripotent stem cell research. IM-12 GMP has been applied in studies related to carrageenan (HY-125474)-induced hind paw edema, TNBS-induced colitis, and acute and chronic myeloid leukemia^{[1][2][3][4][5]}. In Vitro:IM-12 (1 μM; long-term culture) reduces the proliferation rate of human naive pluripotent stem cells and renders cell colonies more compact in morphology. IM-12 upregulates genes associated with oxidative phosphorylation and cell adhesion, downregulates genes related to development and stem cell differentiation, while maintaining the expression of naive pluripotency markers^[1].

IM-12 also enables cells to spontaneously form blastoids that mimic human early blastocysts in 3D culture, and these blastoids can further simulate the developmental process of post-implantation embryos^[1]. In Vivo:IM-12 GMP (0.2×10⁹-5×10⁹ cfu/mouse; p.o.; daily; 3 days) significantly attenuates carrageenan-induced paw oedema in male ICR mice, with the 1×10⁹ cfu/mouse dose demonstrating the most potent inhibition of inflammatory markers and signalling pathways^[2].
IM-12 GMP (1×10⁹ cfu/mouse; p.o.; daily; 3 days) significantly attenuates TNBS-induced colitis in male C57BL/6 mice by suppressing inflammatory markers and NF-κB-STAT3 signalling, with both live and heat-inactivated forms showing efficacy^[2].