PKCθ Inhibitor

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.

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.

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.

CC-90005 is a potent, selective and orally active inhibitor of protein kinase C-θ (PKC-θ), with an IC₅₀ of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC₅₀=4440 nM). CC-90005 can inhibit T cell activation by inhibiting IL-2 expression.

VTX-27 is a selective protein kinase C θ (PKC θ) inhibitor, with K_is of 0.08 nM and 16 nM for PKC θ and PKC δ.

PKC-theta inhibitor 2 is a potent and selective PKC-θ inhibitor with an IC₅₀ value of 18 nM.

TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC₅₀ of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC₅₀s of 13, 68, and 3 nM, respectively.

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.

PKC-theta inhibitor 1 is an orally active and selective ATP-competitive inhibitor of Protein Kinase Cθ (PKCθ), with a K_i value of 6 nM. PKC-theta inhibitor 1 inhibits T-cell-mediated inflammatory responses by suppressing the release of proinflammatory cytokines (IL-2 IC₅₀ = 0.21 μM in anti-CD3/CD28-stimulated PBMCs; IL-17 IC₅₀ = 1 μM in CD3/CD28-stimulated Th17 cells) PKC-theta inhibitor 1 significantly reduces symptoms in mice with ongoing experimental autoimmune encephalomyelitis (EAE). PKC-theta inhibitor 1 can be used for the study of T-cell-mediated inflammatory diseases such as multiple sclerosis.

MS-553 is a potent, ATP-competitive and reversible inhibitor of conventional PKC enzymes with K_is of 5.3 and 10.4 nM for human PKCβ and PKCα, and IC₅₀s of 2.3, 8.1, 7.6, 25.6, 57.5, 314, 808 nM for PKCα, PKCβI, PKCβII, PKCθ, PKCγ, PKC mu and PKCε, respectively.

PKCTheta-IN-2 (compound 14) is a potent and selective PKCθ inhibitor with an IC₅₀ of 0.25 nM. PKCTheta-IN-2 shows good selectivity over a wide range of kinases, including the PKC subfamily (30 kinases). PKCTheta-IN-2 inhibits the IL-2 production in a mouse (IC₅₀ of 682 nM).

GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC₅₀s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC₅₀=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease.

CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a K_i of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with K_is of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent.

PKCTheta-IN-1 (Compound 19) is a selective macrocyclic PKCTheta inhibitor with IC₅₀ value of 0.1 nM.

(Rac)-Aurora A/PKC-IN-1 (Compund 2e) is an orally active Aurora A and PKC (α, β1, β2 and θ) kinase inhibitor. (Rac)-Aurora A/PKC-IN-1 has antiproliferative activity in breast cancer cells in vitro and antimetastatic activity in vivo.

PF-04577806 is a potent, selective and ATP competitive PKC inhibitor. PF-04577806 shows potent inhibitory activity towards PKCα, PKCβI, PKCβII, PKCγ, and PKCθ with IC₅₀s of 2.4 nM, 8.1 nM, 6.9 nM, 45.9 nM, and 29.5 nM, respectively. PF-04577806 can reverse retinal vascular leakage in diabetic rats.

AS2521780 is a novel PKCθ selective inhibitor with an IC₅₀ of 0.48 nM.

PF-03622905 is a potent and ATP-competitive PKC inhibitor with IC₅₀s of 5.6 nM, 14.5 nM, 13 nM, 37.7 nM, and 74.1 nM for PKCα, PKCβI, PKCβII, PKCγ, and PKCθ, respectively. PF-03622905 shows high specificity for PKC over other protein kinases.