KM822

KM822 (100 ns) binds to the allosteric subsite S2-II of human dopamine transporter (hDAT) in the outward-facing open conformation, coordinated by residues W84, R85, F217, D476, H477, and Y548^[1].
KM822 non-competitively inhibits dopamine uptake by human dopamine transporter (hDAT) and reduces the affinity of a controlled tropane alkaloid psychostimulant for hDAT^[1].
KM822 potently and selectively inhibits hDAT-mediated dopamine reuptake with an IC₅₀ of 3.7 μM, showing 30-fold and 50-fold lower potency for hNET and hSERT, respectively, in stably transfected MDCK cells^[2].
KM822 (1-5 μM; 10 min uptake) non-competitively inhibits hDAT-mediated dopamine uptake in transiently transfected COS-7 cells, reducing V_max without significantly altering apparent dopamine K_m at concentrations of 1 μM and 5 μM^[2].
KM822 (10 min pre-incubation at 4°C, followed by 10 min MTSEA-biotin labeling at 4°C) dose-dependently protects the W84C cysteine mutant of hDAT from MTSEA-biotin labeling in transiently transfected HEK-293 cells, with an IC₅₀ of 0.45 μM, confirming direct interaction with the W84 residue in the allosteric site^[2].
KM822 (10 min pre-incubation, followed by 10 min uptake) preferentially binds to the outward-facing conformation of hDAT, as its potency is unchanged in hDAT^Y156F mutants but reduced three-fold in hDAT^Y335A mutants in transiently transfected COS-7 cells^[2].
KM822 (1-5 μM) dose-dependently reduces the potency of Phenethylamine Tropane for inhibiting hDAT-mediated dopamine reuptake in transiently transfected COS-7 cells, increasing phenethylamine tropane's IC₅₀ from 1.2 μM to 4.2 μM and 8.1 μM at concentrations of 1 μM and 5 μM, respectively^[2].
KM822 binds with high affinity to the conserved A2 allosteric pocket in the OFo conformer of C. elegans DAT-1, with no detectable binding to the IFo conformer^[3].
KM822 (10^-3-10³ μM; 10 min pre-incubation) inhibits dopamine uptake via C. elegans DAT-1 (IC₅₀ = 10.4 μM) and human DAT (IC₅₀ = 2.2 μM) in transiently transfected COS-7 cells^[3].
KM822 (20 μM) reduces the affinity of amphetamine for DAT-1 in transiently transfected COS-7 cells, increasing amphetamine's IC₅₀ for dopamine uptake inhibition from 1.1 μM to 3.4 μM^[3].
KM822 (20 μM) reduces the affinity of psychostimulant tropane alkaloid for DAT-1 in transiently transfected COS-7 cells, increasing psychostimulant tropane alkaloid's IC₅₀ for dopamine uptake inhibition from 9.6 μM to 128 μM^[3].
KM822 (150 ns) selectively binds to the allosteric A2 site in the extracellular vestibule of the outward-facing open conformation of human DAT, with distinct residue interactions in two stable binding poses^[4].
KM822 (20 µM; 10 min) directly binds in the vicinity of the W84 residue in human dopamine transporter, confirming interaction with the allosteric A2 site in HEK-293 cells expressing DAT-XC/W84C^[4].
KM822 (10 min) preferentially binds the outward-facing conformation of human dopamine transporter, as its potency is unchanged in COS-7 cells expressing outward-facing shifted Y156F-hDAT but reduced in cells expressing inward-facing shifted Y335A-hDAT^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.