ML-184

ML-184 (CID244033) is a selective GPR55 agonist with an EC₅₀ of 250 nM, more than 100-fold selectivity for GPR55 over GPR35, CB1, and CB2. ML-184 induces ERK1/2 phosphorylation and PKCβII translocation to the plasma membrane via activation of GPR55. ML-184 (CID2440433) increases the proliferation of neural stem cells and promotes neuronal differentiation in vitro^[1][2][3]. In Vitro:ML-184 (1 μM; 48 h) increases the proportion of cells in the S phase and promotes cell proliferation in human neural stem cells (hNSCs), an effect that could be blocked by pretreatment with 5 μM ML193^[2].
ML-184 (1 μM; 10 d) significantly increases the mRNA and protein expressions of neuronal markers βIII-tubulin and microtubule-associated protein 2 (MAP2) in hNSCs, without significant effect on the astrocyte marker S100β^[2]. In Vivo:ML-184 or combined with Sitagliptin (HY-13749) can improve glucose tolerance, insulin sensitivity and insulin secretion response in high-fat-fed (HFF) mice. Islet Ki-67 staining shows that ML-184 increases β-cell proliferation and upregulates pancreatic GPR55, ERK1 and ERK2 gene expression in HFF mice^[3].
ML-184 can increase β-cell area and β-cell mass and reduce α-cell area and mass in high-fat-fed (HFF) mice. ML-184 or combined with Sitagliptin (HY-13749) can significantly increase circulating GIP levels and reduce food intake in mice; it can also increase jejunal GPR55 and JNK1 gene expression levels^[3].