400091  HIF-Hydroxylase Inhibitor, DMOG

N-(Methoxyoxoacetyl)-glycine methyl ester, Dimethyloxalylglycine, HIF Prolyl Hydroxylase Inhibitor II, HIF Aspartyl β-Hydroxylase Inhibitor, HIF Asparanginyl β-Hydroxylase Inhibitor

A cell-permeable 2-OG (2-oxoglutarate) analog that is expected to act as a competitive inhibitor against all 2-OG-dependent dioxygenases. Effectively upregulates normoxia HIF-α transcription activity (effective conc. = 1 mM in cultures) by inhibiting HIF-PH- (HIF-α-prolyl hydroxylase) catalyzed ODD (oxygen-dependent degradation domain) Prolyl hydroxylation (Pro⁵⁶⁴ and Pro⁵³⁰ in HIF-1α and HIF-2α, respectively) and aspartyl/asparanginyl β-hydroxylase-catalyzed CAD Asp hydroxylation (Asn⁸⁰³ and Asn⁸⁵¹ in HIF-1α and HIF-2α, respectively), resulting in a blockage of pVHL (von Hippel-Lindau) ubiquitin ligase complex-mediated HIF-α degradation and a simultaneous promotion of HIF CAD (COOH-terminal activation domain) p300/CBP association. DMOG is also demonstrated to augment artery ligation-induced up-regulation of HIF-1α and FLK (by 100% and 40%, respectively, in 11 days; 8 mg/0.5 ml/animal/i.p.; q.o.d.) in muscle tissues in a murine ischaemic model in vivo.