iGP-1

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.

Cell permeable: yes

Primary Target
mGPDH

Packaged under inert gas

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

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

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

Toxicity: Standard Handling (A)