Uses
Iso-olomoucine is a potent and selective inhibitor of cdc2, cdk and orther cyclin related kinases.
Definition
ChEBI: 2-[[7-methyl-6-[(phenylmethyl)amino]-2-purinyl]amino]ethanol is a thiopurine.
Biological Activity
iso-olomoucine is an inactive stereoisomer of the cdk5 inhibitor olomoucine.cyclin-dependent kinases (cdks) are reported to be key regulators of cell cycle progression whose function/dysfunction has been implicated in cancer, human neurodegenerative diseases, as well as the response of addictive drugs through alteration of postsynaptic dopamine receptor signaling.
in vitro
in a previous study, rat dorsal striatal synaptosomes were incubation with the cdk5 inhibitors roscovitine, olomoucine, and gw8510 or the inactive congener iso-olomoucine, which led to a rapid, concentration-dependent inhibition of specific [3h]da uptake. however, roscovitine was the only inhibitor that did not decrease [3h]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding to dstr dats. roscovitine-induced inhibition of dstr [3h]da uptake was demonstrated by decreased maximal uptake velocity, without a change in cell-surface dat levels. moreover, roscovitine did not enhance [3h]da release mediated by either dat reverse-transport. instead, roscovitine could enhance spontaneous [3h]da outflow and inhibit dat-mediated [3h]da reaccumulation into dstr slices. additionally, in a cdk5-independent manner, iso-olomoucine was able to rapidly inhibit dopamine transporter activity in rat dorsal striatal synaptosomes with a potency similar to that of olomoucine (ic50 ~37 μm) [1]
References
[1] price, d. a.,sorkin, a. and zahniser, n.r. cyclin-dependent kinase 5 inhibitors: inhibition of dopamine transporter activity. molecular pharmacology 76(4), 812-823 (2009).
