5.30655

Mitochondrial GPDH Inhibitor, iGP-1

• 동의어(들): 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
• 실험식(Hill 표기법): C₁₇H₁₅N₃O₃
• CAS Number: 27031-00-1
• Molecular Weight: 309.32
• UNSPSC 코드: 12352200
• NACRES: NA.77

속성

• 분석: ≥98% (HPLC)
• Quality Level: 100
• 형태: solid
• 효능: 6.3 μM IC₅₀
• 제조업체/상표: Calbiochem^®
• 저장 조건: OK to freeze; protect from light
• 색상: beige
• solubility: DMSO: 50 mg/mL
• 저장 온도: 2-8°C

설명

일반 설명

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.

생화학적/생리학적 작용

Cell permeable: yes

Primary Target
mGPDH

포장

Packaged under inert gas

경고

Toxicity: Standard Handling (A)

재구성

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

기타 정보

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

법적 정보

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

안전성 정보

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable