PKCη Inhibitor

Midostaurin (PKC412; CGP 41251) is an orally active, reversible multi-targeted protein kinase inhibitor. Midostaurin inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC₅₀s ranging from 22-500 nM. Midostaurin also upregulates endothelial nitric oxide synthase (eNOS) gene expression. Midostaurin shows powerful anticancer effects.

Rottlerin, a natural product purified from Mallotus Philippinensis, is a specific PKC inhibitor, with IC₅₀ values for PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM, PKCε,η,ζ of 80-100 μM. Rottlerin acts as a direct mitochondrial uncoupler, and stimulates autophagy by targeting a signaling cascade upstream of mTORC1. Rottlerin induces apoptosis via caspase 3 activation. Rottlerin inhibits HIV-1 integration and Rabies virus (RABV) infection.

Sotrastaurin (AEB071) is a potent and orally-active pan-PKC inhibitor, with K_is of 0.22 nM, 0.64 nM, 0.95 nM, 1.8 nM, 2.1 nM and 3.2 nM for PKCθ, PKCβ, PKCα, PKCη, PKCδ and PKCε, respectively.

Afuresertib (GSK2110183) is an orally bioavailable, selective, ATP-competitive and potent pan-Akt kinase inhibitor with K_is of 0.08/2/2.6 nM for Akt1/Akt2/Akt3, respectively.

Ruboxistaurin (LY333531) is an orally active, selective PKC beta inhibitor (K_i=2 nM). Ruboxistaurin exhibits ATP dependent competitive inhibition of PKC beta I with an IC₅₀ of 4.7 nM. Ruboxistaurin inhibits PKC beta II with an IC₅₀ of 5.9 nM.

Ruboxistaurin (LY333531) hydrochloride is an orally active, selective PKC beta inhibitor (K_i=2 nM). Ruboxistaurin hydrochloride exhibits ATP dependent competitive inhibition of PKC beta I with an IC₅₀ of 4.7 nM. Ruboxistaurin hydrochloride inhibits PKC beta II with an IC₅₀ of 5.9 nM.

Afuresertib hydrochloride (GSK 2110183 hydrochloride) is an orally bioavailable, selective, ATP-competitive and potent pan-Akt kinase inhibitor with K_is of 0.08/2/2.6 nM for Akt1/Akt2/Akt3 respectively.

Hu7691 is an orally active, selective Akt inhibitor with IC₅₀s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 inhibits tumor growth and enables decrease of cutaneous toxicity in mice.

PF-4950834 is a potent, selective, orally bioavailable, ATP-competitive rho kinase inhibitor with IC₅₀ values of 8.35 nM and 33.12 nM against ROCK2 and ROCK1, respectively. PF-4950834 inhibits neutrophil migration.

Ruboxistaurin (LY333531) mesylate is an orally active, selective and ATP competitive PKCβ inhibitor with IC₅₀ values of 4.7 and 5.9 nM for PKCβI and PKCβII, respectively. Ruboxistaurin mesylate can be used for the research of eye disorders, heart failure and diabetes.

Hu7691 free base is an orally active, selective Akt inhibitor with IC₅₀s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice.

PS315, a derivative of PS48 (HY-15967), is an allosteric PKC inhibitor by binding to the PIF-pocket of aPKC and inducing a displacement of the active site residue Lys111. PS315 inhibits the full-length and catalytic domain constructs of PKC_ζ (IC₅₀=10 μM) and PKC_η (IC₅₀=30 μM). PS315 has anti-cancer activity.

Balanol (Ophiocordin; Azepinostatin) is a potent and ATP competitive PKC/PKA inhibitor against human PKC isozymes α, β-I, β-II, γ, δ, ε, η (IC₅₀s=4-9 nM) and ζ (IC₅₀=150 nM). Balanol also blocks the phosphorylation of cyclic AMP response element-binding protein (CREB) and myristoylated alanine-rich C kinase substrate (MARCKS). Balanol can be isolated from the fungus Verticillium balanoides.