Halofuginone (RU-19110) is a less-toxic form of Febrifugine, which is isolated from the plant Dichroa febrifuga[1]. Halofuginone inhibits prolyl-tRNA synthetase in an ATP-dependent manner with a Ki of 18.3 nM[2]. Halofuginone attenuates osteoarthritis (OA) by inhibition of TGF-β activity[3].
O-Desmethyl Midostaurin (CGP62221; O-Desmethyl PKC412) is the active metabolite of Midostaurin (HY-10230) via cytochrome P450 liver enzyme metabolism. O-Desmethyl Midostaurin can be used as an indicator for Midostaurin metabolism in vivo[1]. Midostaurin is a multi-targeted protein kinase inhibitor with IC50 ranging from 22-500 nM.
ITD-1 is the first selective TGFβ inhibitor with an IC50 of 460 nM.
WF-536 is an orally active inhibitor of Rho-associated coiled-coil-containing protein kinase (ROCK). WF-536 has tumor anti-metastatic activity. WF-536 can be used for the research of cancer[1].
Pentanoic acid, a short-chain fatty acid, is a product of bacterial metabolism and are associated with allergic skin disorders. Pentanoic acid activates ROCK signaling pathway.
Y-33075 dihydrochloride is a selective ROCK inhibitor derived from Y-27632, and is more potent than Y-27632, with an IC50 of 3.6 nM.
β-Amyloid (1-40) is a primary protein in plaques found in the brains of patients with Alzheimer's disease.
GSK317354A is a ROCK and GRK inhibitor. GSK317354A can be used for heart failure and Parkinson’s disease research[1].
LY3200882 is a novel and highly selective inhibitor of TGF-β receptor type 1 (TGFβRI).
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[1].
LDN-212854 is a novel BMP inhibitor that exhibits substantially greater selectivity for BMP versus the TGF-β type I receptors; possesses a bias towards ALK2(IC50=1.3 nM) versus ALK1 and ALK3 compared to other inhibitors.IC50 value: 1.3 nM [1]Target: ALK2 In vitro, LDN-212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling, transcriptional activity and function. LDN-212854 potently inhibitsheterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva.
H-1152 dihydrochloride is a membrane-permeable and selective ROCK inhibitor, with a Ki value of 1.6 nM, and an IC50 value of 12 nM for ROCK2.
Mitoxantrone dihydrochloride is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM.
ROCK-IN-1 is a potent inhibitor of ROCK, with an IC50 of 1.2 nM for ROCK2.
Bisindolylmaleimide I (GF109203X) is a highly selective, cell-permeable, and reversible protein kinase C (PKC) inhibitor with a Ki of 14 nM.
Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative isolated from plants of the Genus Daphne, is a protein kinase inhibitor, with IC50s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively[1][2]. Daphnetin (7,8-dihydroxycoumarin) is a secondary metabolite of plants used in folk medicine to counter inflammatory and allergic diseases, also has been clinically used in the treatment of coagulation disorders, rheumatoid arthritis with anti-malarian and anti-pyretic properties[3].
ROCK2-IN-2 is a selective ROCK2 inhibitor extracted from patent US20180093978A1, Compound A-30, has an IC50 of <1 μM.
CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis 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[1].
N-Desmethyltamoxifen hydrochloride is the major metabolite of tamoxifen in humans. N-Desmethyltamoxifen, a poor antiestrogen, is a ten-fold more potent protein kinase C (PKC) inhibitor than Tamoxifen. N-Desmethyltamoxifen hydrochloride is also a potent regulator of ceramide metabolism in human AML cells, limiting ceramide glycosylation, hydrolysis, and sphingosine phosphorylation[1][2][3].
p32 inhibitor M36 (M36) is a p32 mitochondrial protein inhibitor, which binds directly to p32 and inhibits p32 association with LyP-1[1].
Bisindolylmaleimide VIII acetate (Ro 31-7549 acetate) is a potent and selective protein kinase C (PKC) inhibitor with an IC50 of 158 nM for rat brain PKC. Bisindolylmaleimide VIII acetate has IC50s of 53, 195, 163, 213, and 175 nM for PKC-α, PKC-βI, PKC-βII, PKC-γ, PKC-ε, respectively[1]. Bisindolylmaleimide VIII acetate facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases[2].
Trimethylamine N-oxide is a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients. Trimethylamine N-oxide induces inflammation by activating the ROS/NLRP3 inflammasome. Trimethylamine N-oxide also accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis by activating the TGF-β/smad2 signaling pathway[1][2][3].
SLx-2119 is a selective inhibitor of ROCK2 with an IC50 of 105 nM.
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[1][2].
Ingenol Mebutate is an active ingredient in Euphorbia peplus, acts as a potent PKC modulator, with Kis of 0.3, 0.105, 0.162, 0.376, and 0.171 nM for PKC-α, PKC-β, PKC-γ, PKC-δ, and PKC-ε, respectively, and has antiinflammatory and antitumor activity.
ZINC00881524 is a ROCK inhibitor.
Fasudil (HA-1077; AT877) hydrochloride semihydrate is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an Ki 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 semihydrate is also a potent Ca2+ channel antagonist and vasodilator[1][2][3].