Dopamine D2 Receptor Antagonist, SB269652

A tetrahydroisoquinoline-7-carbonitrile based compound that acts as a negative allosteric modulator of dopamine D2 receptor (estimated affinity (K_b) = 145-416 nM in GTP γS binding and in cell based functional assays). Its allosteric action requires D2R dimers. Shown to significantly reduce dopamine potency (8 to 16 fold), but acts as a partial antagonist and allows some dopamine action to remain. Displays features similar to orthosteric D2R antagonists and its highly stable tetrahydroisoquinoline (THIQ) moiety occupies the orthosteric site. Also exhibits bitopic mode of interaction with D2R. Binds to one promoter of D2R dimer in a bitopic mode and modulates the action of dopamine at the other. A G2A mutation in D2R causes a 9-fold reduction in its affinity and 5-fold decrease in negative cooperativity.

Dopamine D2 Receptor Antagonist, SB26965, is a negative allosteric modulator of dopamine D2 receptor (estimated affinity (K_b) = 145 - 416 nM in GTPgS binding and in cell based functional assays).

Primary Target
D2

Reversible: yes

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Lane, J., et al. 2014. Nat. Chem. Biol.10, 745.

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

Toxicity: Standard Handling (A)