5.30655

Mitochondrial GPDH Inhibitor, iGP-1

• Sinonimo/i: Mitochondrial GPDH Inhibitor, iGP-1, N-(4-(1H-Benzoimidazol-2-yl)-phenyl)-succinamic acid, Mitochondrial sn-Glycerol-3-Phosphate Dehydrogenase Inhibitor, mGPDH Inhibitor, inhibitor of m GPDH 1, iGP1, N-(4-(1H-Benzoimidazol-2-yl)-phenyl)-succinamic acid, Mitochondrial sn-Glycerol-3-Phosphate Dehydrogenase Inhibitor, mGPDH Inhibitor, inhibitor of mGPDH 1, iGP1
• Formula empirica (notazione di Hill): C₁₇H₁₅N₃O₃
• Numero CAS: 27031-00-1
• Peso molecolare: 309.32
• Codice UNSPSC: 12352200
• NACRES: NA.77

Proprietà

• Saggio: ≥98% (HPLC)
• Livello qualitativo: 100
• Forma fisica: solid
• Potenza: 6.3 μM IC₅₀
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: beige
• Solubilità: DMSO: 50 mg/mL
• Temperatura di conservazione: 2-8°C

Descrizione

Descrizione generale

A cell-permeable benzimidazolyl-phenylamidosuccinate compound that acts as a potent, selective, and dose-dependent inhibitor against mitochondrial, but not cytosolic, sn-glycerol-3-phosphate dehydrogenase (IC₅₀ against mGPDH = 6.3 µM). Shown to directly interact with a single, allosteric binding site on mGPDH and displays mixed type of inhibition kinetics (K_ic = 9.5 µM and K_iu = 14.6 µM, glycerol phosphate/GP-competitive against free and GP-uncompetitive against GP-bound mGPDH). Reduces H₂O₂ production by IQ site (IC₅₀ = 13.6 µM) and inhibits ΔΨm driven by low concentrations of succinate (0.5 µM), but does not inhibit glutamate-, malate-, pyruvate-, or palmityoylcarnitine-driven ΔΨm. Does not prevent pyruvate uptake into cells or mitochondria and has no direct effect on Glycolysis in synaptosomes.

A cell-permeable thiadiazolyl-butyl-pyridazinyl compound that displays increased fluorescence with acidified pH (by 8-fold from pH 7.0 to 1.5; Ex 342 nm & Em 378 nm) and selectively inhibits mitochondrial sn-glycerol 3-phosphate (GP) dehydrogenase (mGPDH) activity (IC₅₀ = 6.3 µM by DCPIP assay using rat skeletal muscle mitochondria preparation with 1 µ Ca²⁺), but not cytosolic GPDH (up to 80 µM using rabbit cGPDH), by targeting free mGPDH in a GP-competitive manner (K_icK_iu2-dependent complex I activity and little potency toward unbiquinol/QH₂-dependent complex III activity, nor FMN-dependent complex I or II activity. Under conditions where Lactate dehydrogenase-mediated NAD⁺ generation is blocked by Oxamate in murine cortical synaptosome preparations, a small but significant dependence on mGPDH-mediated GP shuttle for NAD⁺ generation to support the high glycolytic demand for pyruvate generation from glucose (15 mM) is reported, as evidenced by a more pronounced mitochondrial respiration inhibition in the presence of FCCP and Oligomycin (4 µg/mL; Cat. No. 495455) with the combined treatment of 0.5 mM aminooxyacetate (AOA) and 100 µM iGP-1 than with AOA alone.

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
mGPDH

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Standard Handling (A)

Ricostituzione

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Altre note

Orr, A.L., et al. 2014. PLoS One9, e89938.

Note legali

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable