GSK2141795 (hydrochloride)

Uprosertib hydrochloride (GSK2141795 hydrochloride) is a potent and selective pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.

Research Areas >> Cancer

Akt1:180 nM (IC50)

Akt2:328 nM (IC50)

Akt3:38 nM (IC50)

CDK7:2100 nM (IC50)

ROCK1:1570 nM (IC50)

ROCK2:1850 nM (IC50)

Uprosertib inhibits Akt1/2/3 with the Kd values of 16/49/5 nM, respectively. Uprosertib potently inhibits only the PKC family members PRKACA and PRKACB as well as the cGMP-dependent protein kinase PRKG1 aqpart from the Akts. Protein targets that bind Uprosertib in the lysate show a dose-dependent reduction in binding to the kinobeads, while proteins unaffected by the drug show no reduction in binding[1].

For selectivity profiling experiments, the lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or Uprosertib) on an end-over-end shaker for 45 min at 4°C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4°C, for both qualitative and quantitative experiments. The beads are washed with 1×CP buffer and collected by centrifugation. Bound proteins are eluted with 2×NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.

[1]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.

SB203580 | MK-2206 2HCl | SC79 | Capivasertib (AZD5363) | Honokiol | AKT inhibitor VIII | GDC-0068 | GSK690693 | Uprosertib | 1,3-Dicaffeoylquinic acid | TIC10 | Triciribine | Perifosine (KRX-0401) | afuresertib | A-443654