DMOG

DMOG is a competitive and cell-permeable hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, as well as an activator of hypoxia-inducible factor-1α (HIF-1α)^[1]. DMOG stabilizes HIF-1α and prevents its prolyl hydroxylation-mediated degradation by inhibiting HIF-PH enzymatic activity, thereby stabilizing HIF-1α and activating downstream target gene expression at both the cellular and animal levels^[2]. DMOG is commonly used in research areas including HIF signaling pathway regulation, ischemia-reperfusion injury protection, angiogenesis, and neuroprotection^[3,4].

In vitro, treatment of rat bone marrow mesenchymal stromal cells (BM-MSCs) with DMOG (500, 1000μM) for 72h significantly upregulated C-X-C chemokine receptor type 4 (CXCR4) protein expression compared with the control group^[5]. DMOG (0.5mM) pretreatment of PC12 and HCT116 cells for 0.5h significantly inhibited mitochondrial respiration and activated glycolytic activity^[6].

In vivo, Sprague-Dawley rats exposed to chronic hypoxia (10% O₂) and treated with DMOG (100mg/kg; once daily; i.p.) for 4 weeks showed significant stabilization of myocardial HIF-1α protein levels^[7]. In BALB/c mice pretreated with DMOG (8mg/mouse; i.p.) 2h prior to lipopolysaccharide (LPS)-induced endotoxic shock, DMOG significantly improved survival rate, decreased serum TNF-α levels, and increased IL-10 levels^[8].

References:

[1] Zhang Y, Cai W, Ren Z, et al. Chiral supramolecular hydrogel loaded with dimethyloxalyglycine to accelerate chronic diabetic wound healing by promoting cell proliferation and angiogenesis[J]. Gels, 2022, 8(7): 437.

[2] Ding H, Gao Y S, Wang Y, et al. Dimethyloxaloylglycine increases the bone healing capacity of adipose-derived stem cells by promoting osteogenic differentiation and angiogenic potential[J]. Stem cells and development, 2014, 23(9): 990-1000.

[3] Sen T, Sen N. Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury[J]. Neuropharmacology, 2016, 107: 79-88.

[4] Ockaili R, Natarajan R, Salloum F, et al. HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2005, 289(2): H542-H548.

[5] Yinfei W, Aiping J, Chao F, et al. DFO and DMOG up-regulate the expression of CXCR4 in bone marrow mesenchymal stromal cells[J]. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 2013, 68(10): 835-838.

[6] Zhdanov A V. HIF-independent inhibition of mitochondrial function by DMOG: Immediate–early effects and long-term consequences[J]. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 2014.

[7] Zhang S, Ma K, Liu Y, et al. Stabilization of Hypoxia-inducible Factor by DMOG Inhibits Development of Chronic Hypoxia–Induced Right Ventricular Remodeling[J]. Journal of cardiovascular pharmacology, 2016, 67(1): 68-75.

[8] Hams E, Saunders S P, Cummins E P, et al. The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells[J]. Shock, 2011, 36(3): 295-302.