MRS2693

MRS2693 is a selective P2Y6 receptor agonist. MRS2693 exerts biological effects by activating the Gq-coupled P2Y6 receptor, the ERK1/2 pathway, and the P2RY6-PLCB3-CAMKK2-PRKAA1-ULK1 signaling cascade. MRS2693 attenuates TNFα-induced NF-κB activation, stabilizes XIAP via AKT-mediated phosphorylation, induces autophagy, and reactivates PRKAA1. MRS2693 can be used in research on diseases including skeletal muscle ischemia/reperfusion injury, TNFα-induced skeletal muscle apoptosis, chronic myelomonocytic leukemia, colorectal cancer, and dry eye disease^[1][2][3][4]. In Vitro: MRS2693 (10-30 μM; 4 h-4 days) restores autophagy and normal differentiation of primary CD14⁺CD24^- monocytes from a CMML patient co-cultured with CD14^-CD24⁺ immature granulocytes, via reactivation of PRKAA1, while 10 μM MRS2693 partially increases PRKAA1 expression^[2].
MRS2693 (1.5 μM; 15 min pre-incubation; continued during 4 h TNFα/CHX treatment and subsequent 16 h incubation) protects HT-29 colon carcinoma cells from TNFα-induced apoptosis by stabilizing XIAP via AKT-mediated phosphorylation, resulting in reduced PARP cleavage^[3].
MRS2693 (1.5 μM; 30 min pre-incubation; continued during 24 h 5-FU treatment) induces resistance to 5-FU cytotoxicity in mouse CRC-derived tumoroids, preserving both tumoroid viability and proliferative cell activity^[3]. In Vivo: MRS2693 (1 mg/kg; i.p.; single injection 2 hours before ischemia induction) significantly reduces skeletal muscle ischemia/reperfusion injury in C57BL6 mice, lowering serum CK activity by ~72.6% and EBD-stained injured muscle area by ~63.2%^[1].