Dorsomorphin

• CAT Number: I005212
• CAS Number: 866405-64-3
• Molecular Formula: C₂₄H₂₅N₅O
• Molecular Weight: 399.49
• Purity: ≥95%
• Target: AMPK
• Solubility: 10 mM in DMSO (with heating)； 5 mM in ethanol (with heating)
• Storage: Store at -20C
• IC50: 109 nM (Ki for AMPK)
• InChI: InChI=1S/C24H25N5O/c1-2-12-28(13-3-1)14-15-30-22-6-4-19(5-7-22)21-16-26-24-23(17-27-29(24)18-21)20-8-10-25-11-9-20/h4-11,16-18H,1-3,12-15H2
• InChIKey: XHBVYDAKJHETMP-UHFFFAOYSA-N
• SMILES: C1CCN(CC1)CCOC2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC=C5)N=C3

Dorsomorphin(Compound C; BML-275) has been shown to act as a potent and selective inhibitor of AMPK (AMP-activated protein kinase; Ki = 109 nM), induced by AICAR and metformin; also inhibits the bone morphogenetic protein type 1 receptors ACTR-I (ALK2), BMPR-IA (ALK3), and BMPR-IB (ALK 6).IC50 value: 109 nM (Ki for AMPK)Target: AMPKin vitro: Compound C treatment of MCF7 cells led to Bax redistribution from the cytoplasm to mitochondria and cell death.ceramide synthase 5 (LASS/CerS 5) is involved in Compound C-induced ceramide upregulation. Downregulation of LASS/CerS 5 was found to attenuate Compound C-mediated ceramide production, Bax redistribution, and cell death [1]. compound C prevented UPR marker glucose-regulated protein 78 (GRP78) accumulation and exerted enhanced cytotoxicity during glucose deprivation. compound C had a unique mode of action to suppress the transcriptional activation of UPR-targeted genes, as compared with the classic UPR inhibitors versipelostatin and biguanides. Surprisingly, the UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition [2]. Compound C-mediated inhibition of AMPK and raptor in U251 cells was associated with paradoxical decrease in phosphorylation of AMPK/raptor-repressed mTOR, a major negative regulator of autophagy, and its downstream target p70S6K [3].in vivo:

Reference

[1]. Jin J, et al. AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells. J Lipid Res. 2009 Dec;50(12):2389-97.
[2]. Saito S, et al. Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling. PLoS One. 2012;7(9):e45845.
[3]. Vucicevic L, et al. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. Autophagy. 2011 Jan;7(1):40-50.