PKCε Translocation Inhibitor II, PKCe141

A cell-permeable non-peptidic thienoquinoline modeled after pharmacophore feature derived from the non-permeant EAVSLKPT (Cat. no. 539522) and found to selectively inhibit PKCε-RACK2, but not PKCβII-RACK1, interaction (IC₅₀ = 5.9 µM; [RACK2-MBP] = 500 ng/50 µL or 62.5 nM) and suppress PKCε, but not PKCδ membrane translocation induced by PMA/TPA (Cat. nos. 500582 & 524400) in serum-starved PC-3 cultures (20 or 50 µM PKCe141 added 30 min prior to 50 or 100 nM TPA stimulation for 5 min). Likewise, PKCe141 is demonstrated to inhibit Elk-1 activation domain (aa 307-427) phosphorylation-dependent HeLa luciferase reporter (HLR) transcription (IC₅₀ = 11.2 µM) as well as MARCKS S152/S156 phosphorylation in serum-starved HeLa cells (50 µM) upon TPA stimulation without cytotoxicity (up to 50 µM for 72 h by SRB assay). PKCe141 does not inhibit cellular PKCε phosphorylation and exhibits little potency against PKC kinase activity (% inhibition at 50 µM/150 ng PKC = 23/η, 18/βI, 17/α, 12/ε, 11/γ, 9/ι, 6/δ & θ, 1/βII, 0/ζ; [ATP] = 40 µM; substrate [PKCα 19-31] = 50 µM), while more significant inhibition is seen against 5 other kinases among a panel of 109, the observed potency (% inhibition at 50 µM = 73/RSK2, 58/BTK, 54/PIM3, 51/NUAK1, 45/ERK1) is less than that toward PKCε-RACK2 interaction. Also reported to suppress active PKCε-dependent HeLa migration (25 µM for 24 h) and inhibit VEGF-induced angiogenesis in chicken eggs (10 ng VEGF & 10 ng PKCe141).

A cell-permeable, non-toxic thienoquinoline compound that dose-dependently inhibits PKCε-RACK2 interaction (IC₅₀ = 5.9 µM). Shown to occupy PKCε to RACK2 binding site in a reversible manner and block cellular phosphorylation of MARCKS and Elk-1 (IC₅₀ = 11.2 µM in HeLa cells). Prevents TPA-induced PKCε translocation to the plasma membrane, and reduces PKCε-induced cell migration, invasion and suppresses angiogenesis. Displays desireable selectivity in a 109-kinase panel, and at higher concentrations affects PKCα, βI and ζ (~80% at 50 µM) and ERK1, RSK2, NUAK1, PIM3 & BTK (>50% at 25 µM) activities.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
PKCε

Reversible: yes

Packaged under inert gas

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

Rechfeld, F., et al. 2014. J. Med. Chem.57, 3235.

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

Toxicity: Standard Handling (A)