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阻害剤
ターゲット | 低分子化合物 | 性質 |
PKC (α, β, γ, δ) | IC50:7 nM (PKCα)、7 nM (PKCβ)、6 nM (PKCγ)、10 nM (PKCδ)、60 nM (PKCζ)、20,000 nM (PKCμ)1 | |
PKC (α, β, γ, ε) | IC50:50 nM (PKCβ)3 PKCβ に特に高い選択性を示す。増殖因子の分泌と血小板凝集を促す3。 | |
PKC (α, γ, η) | IC50:2 nM (PKCα)4、5 nM (PKCγ)、4 nM (PKCη)5 上記以外の PKC アイソザイムへの阻害活性は弱い。 | |
PKC (α, βI, βII, γ) | IC50:5-70 nM6 高い選択性を示す PKC 競合阻害剤6。 | |
PKC (α, β1) | IC50:2.3 nM (PKCα)、6.2 nM (PKCβ1)7 Ca2+ 非依存性 PKC よりも、Ca2+ 依存性 PKC に高い選択性を示す阻害剤8。 | |
PKCζ | PKCζ 調節ドメイン会合性ミリストイル化ペプチド9で、非典型 PKC 阻害剤。PKC の細胞内局在化を阻害する10。 | |
PKCβ | IC50:4.7 nM (PKCβ1)、PKC 5.9 nM (PKCβ1)11 競合的かつ可逆的 PKCβ 選択的阻害剤12、13。 | |
PKC (α, β1, βII, γ, ε) | IC50:22 nM PKC、28 nM (PKCα)、13 nM (PKCβ1)、11 nM (PKCβII)、32 nM (PKCγ)、25 nM (PKCε)14 細胞透過性、競合的 PKC 阻害剤15。Staurosporine アナログ。 | |
PKC (α, β1, βII, γ, ε) | IC50:21 nM (PKC)、9 nM (PKCα)、28 nM (PKCβ1)、31 nM (PKCβ2)、37 nM (PKCγ)、108 nM (PKCε)14 細胞透過性、PKC選択的阻害剤。T 細胞の活性化を妨害する16。 | |
PKC (α, β1, δ, η, θ) | Ki:0.95 nM (PKCα)、0.64 nM (PKCβ1)、2.1 nM (PKCδ)、1.8 nM (PKCη)、0.22 nM (PKCθ)17 特に T 細胞に対する免疫抑制剤としての性質を持つ PKC 阻害剤17、18。 | |
PKC (α, β, γ, δ, ε, η, ζ) | IC50:3-6 μM (δ)、30-42 μM (α, β, γ)、80-100 μM (ε, η, ζ)19 細胞透過性可逆的阻害剤。5 分以内に効果を示す20。 | |
PKCμ | IC50:7 nM (PKCμ)21、25 nM (PKC)22 ATP 競合 PKC 阻害剤23。Staurosporine アナログ。 | |
PKC | PKC の活性と細胞内移動を阻害24。活性酸素(ROS)を発生させ、アポトーシスを誘導する25。 | |
PKC の活性と細胞内移動を阻害24。活性酸素(ROS)を発生させ、アポトーシスを誘導する25。 | ||
IC50:50 nM26 光により活性化される PKC 阻害剤。がん細胞の増殖を阻害する26。 | ||
IC50:660 nM27 グループ A と B に属する PKC アイソフォームの選択的阻害剤28。 | ||
IC50:40 μM29 リゾスフィンゴ脂質 PKC 阻害剤。ビンカ・アルカロイドやアントラサイクリンの活性を高める29。 | ||
IC50:3 μM30 もしくは 0.8 μM31 PKC の触媒活性サイトに結合。MgATP で Melittin-PKC 相互作用を妨害することができる30。 | ||
PKC への作用により、腫瘍形成を抑制できる32。増殖抑制の IC50 は 10 nM。FLT3 変異性の急性骨髄性白血病(acute myeloid leukemia:AML)や進行性全身性肥満細胞症に適用33。 |
PKC 活性化剤
低分子化合物 | 性質 |
nM オーダーの PKC 結合親和性を示す強力なアゴニスト。在来型と新型の PKC アイソザイムに結合34。 | |
広域な PKC アクチベーター。プロアポトーシス促進作用と免疫刺激効果を示す35、36。 | |
PKC の下流ターゲットのリン酸化を促進し活性化。血管平滑筋の収縮を誘導37、38。 | |
Ca2+-ATPase を活性化する可逆的 PKC アクチベーター39。DAG よりも強力に PKC を活性化できる。 | |
PKC および NF-κB の活性化剤41。カルシウム/カルシニューリン・シグナルに相乗効果を与える42。 | |
PKC リン酸化を誘導する PKC アクチベーター。Ca2+ 依存的に PKC を活性化43、44。 |
参考文献
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