PKC Inhibitor

Forskolin (Coleonol) is a potent adenylate cyclase activator with an IC₅₀ of 41 nM and an EC₅₀ of 0.5 μM for type I adenylyl cyclase. Forskolin is also an inducer of intracellular cAMP formation. Forskolin induces differentiation of various cell types and activates pregnane X receptor (PXR) and FXR. Forskolin exerts a inotropic effect on the heart, and has platelet antiaggregatory and antihypertensive actions. Forskolin also induces autophagy.

Staurosporine is a potent, ATP-competitive and non-selective inhibitor of protein kinases with IC₅₀s of 6 nM, 15 nM, 2 nM, and 3 nM for PKC, PKA, c-Fgr, and Phosphorylase kinase respectively. Staurosporine also inhibits TAOK2 with an IC₅₀ of 3 μM. Staurosporine is an apoptosis inducer.

Go 6983 is a pan-PKC inhibitor against for PKCα, PKCβ, PKCγ, PKCδ and PKCζ with IC₅₀ of 7 nM, 7 nM, 6 nM, 10 nM and 60 nM, respectively.

Mitoxantrone hydrochloride liposome is a liposome-encapsulated Mitoxantrone hydrochloride (HY-13502A) (a topoisomerase II inhibitor). Compared to regular Mitoxantrone hydrochloride, Mitoxantrone hydrochloride liposome enhances antitumor activity and prolongs drug circulation time in the body.

Variegatic acid is a secondary metabolite derived from basidiomycete fungi. Variegatic acid is a PKCβ1 inhibitor with an IC₅₀ of 36.2 μM. Variegatic acid inhibits antigen- or calcium ionophore-induced β-hexosaminidase release (IC₅₀ values of 10.4 μM and 22.2 μM, respectively) and TNF-α secretion (IC₅₀ values of 16.8 μM and 20.1 μM, respectively). Variegatic acid suppresses the enzymatic activity of calcium-activated PKCβ1 and reduces Fe(III) to Fe(II) in a pH-dependent manner, enabling the generation of hydroxyl radicals (·OH) through reaction with H₂O₂, which facilitates the degradation of lignocellulose. Variegatic acid is useful for studying biological degradation and allergic responses.

NA 0345 is a PKC inhibitor with IC₅₀ values of 70 nM and 110 nM in the presence and absence of 12-O-tetradecanoyl-13-acetate, respectively. NA 0345 inhibits PKC and selectively suppresses the positive inotropic effect mediated by α₁-adrenergic receptors.

Mitoxantrone is a potent topoisomerase II inhibitor. Mitoxantrone also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM. Mitoxantrone induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone shows antitumor activity. Mitoxantrone also has anti-orthopoxvirus activity with EC₅₀s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively.

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.

Fasudil (HA-1077; AT877) Hydrochloride is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil Hydrochloride is also a potent Ca²⁺ channel antagonist and vasodilator.

Bisindolylmaleimide I (GF109203X) is a cell-permeable and reversible PKC inhibitor (IC₅₀ of 20 nM, 17 nM, 16 nM, and 20 nM for PKCα, PKCβI, PKCβII, and PKCγ. Bisindolylmaleimide I is also a GSK-3 inhibitor.

Verbascoside is isolated from Acanthus mollis, acts as an ATP-competitive inhibitor of PKC, with an IC₅₀ of 25 μM, and has antitumor, anti-inflammatory and antineuropathic pain activity.

D-erythro-Sphingosine (Erythrosphingosine) is a very potent activator of p32-kinase with an EC₅₀ of 8 μM, and inhibits protein kinase C (PKC). D-erythro-Sphingosine (Erythrosphingosine) is also a PP2A activator.

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.

Hypericin is a naturally occurring substance found in Hyperlcurn perforatum L. Hypericin is an inhibitor of PKC (protein kinase C), MAO (monoaminoxidase), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450). Hypericin shows antitumor, antiviral, antidepressive activities, and can induce apoptosis.

Mitoxantrone dihydrochloride is a potent topoisomerase II inhibitor. Mitoxantrone dihydrochloride also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM. Mitoxantrone dihydrochloride induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone dihydrochloride shows antitumor activity. Mitoxantrone dihydrochloride also has anti-orthopoxvirus activity with EC₅₀s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively.

Darovasertib (LXS196) is a potent, selective and orally active protein kinase C (PKC) inhibitor, with IC₅₀ values of 1.9 nM, 0.4 nM and 3.1 μM for PKCα, PKCθ and GSK3β, respectively. Darovasertib has the potential for uveal melanoma research.

Enzastaurin (LY317615) is a potent, selective, and CNS-penetrant PKCβ inhibitor with an IC₅₀ of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε.

CMPD101 is a potent, highly selective and membrane-permeable small-molecule inhibitor of GRK2/3 with IC₅₀ of 18 nM and 5.4 nM, respectively. CMPD101 exhibits less selectively against GRK1, GRK5, ROCK-2 and PKCα with IC₅₀s of 3.1 μM , 2.3 μM, 1.4 μM and 8.1 μM, respectively. CMPD101 can be used for the study of heart failure.

Go6976 is a Protein Kinase C (PKC) inhibitor, with an IC₅₀ of 20 nM.