TGF-β/Smad

RKI-1313 is a negative control for RKI-1447 which is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer.

Thiazovivin is a selective inhibitor of Rho-associated kinase (ROCK).

RKI-1447 dihydrochloride is a selective inhibitor of Rho-associated kinase (ROCK), exhibiting IC50 values of 14.5 nM and 6.2 nM for ROCK1 and ROCK2, respectively. This compound effectively suppresses the growth of colorectal carcinoma cells while inducing apoptosis, making it a valuable tool for research in cancer biology and therapeutics targeting ROCK signaling pathways.

PT-262 is a selective ROCK inhibitor with an IC50 of approximately 5 μM. This compound induces loss of mitochondrial membrane potential and enhances caspase-3 activation, leading to apoptosis. PT-262 also inhibits phosphorylation of ERK and CDC2 through a p53-independent mechanism, disrupts cytoskeletal dynamics, and impairs cell migration. Its efficacy in promoting anti-cancer activity makes PT-262 a valuable reagent for cancer research.

Y-27632 hydrochloride hydrate is a selective inhibitor of Rho-associated protein kinases (ROCK-I and ROCK-II), exhibiting ATP-competitive activity with IC50 values of 220 nM and 300 nM, respectively. This compound has been shown to reduce Doxorubicin-induced apoptosis in human cardiac stem cells and suppress apoptosis in dissociation-induced murine prostate stem/progenitor cells. Additionally, Y-27632 hydrochloride hydrate enhances the differentiation of human induced pluripotent stem cells (hIPSCs) towards a mesendodermal lineage by modulating epithelial-mesenchymal transition.

PKCβ Inhibitor 1 is a highly selective, ATP-competitive inhibitor targeting protein kinase C beta (PKCβ) with IC50 values of 21 nM for PKCβ1 and 5 nM for PKCβ2. This compound demonstrates over 60-fold selectivity for PKCβ2 compared to other PKC isozymes such as PKCα, PKCγ, and PKCε. It is a valuable tool for investigating the roles of PKCβ in various signaling pathways and its implications in diseases such as cancer and diabetes.

DJ4 is an ATP-competitive inhibitor of ROCK1/2 and MRCKα/β, with IC₅₀ values of 5 nM and 50 nM for ROCK1 and ROCK2, and 10 nM and 100 nM for MRCKα and MRCKβ, respectively. It blocks stress fiber formation and induces apoptosis, making it a valuable compound for cancer research.

Cotosudil is a ROCK kinase inhibitor that can be used in research related to glaucoma and ocular hypertension. It functions by reducing intraocular pressure through modulation of aqueous humor outflow.

THK01 is a potent and selective ROCK2 inhibitor, with IC₅₀ values of 5.7 nM for ROCK2 and 923 nM for ROCK1. It inhibits breast cancer metastasis by targeting the ROCK2–STAT3 signaling pathway and is suitable for research in breast cancer.

HSD1590 is a potent inhibitor of Rho-associated protein kinases, with IC₅₀ values of 1.22 nM for ROCK1 and 0.51 nM for ROCK2. It exhibits strong binding affinity to ROCK isoforms (K\_d < 2 nM) and demonstrates low cytotoxicity, making it suitable for further research applications.

CRT0066854 is a potent and selective inhibitor of atypical protein kinase C (PKC) isoenzymes. It inhibits full-length PKCι, PKCζ, and ROCK-II with IC₅₀ values of 132 nM, 639 nM, and 620 nM, respectively.

AS1892802 is a potent, orally active, and highly selective inhibitor of Rho-associated kinase (ROCK). It exhibits a rapid onset of antinociceptive effect, comparable to that of Tramadol and Diclofenac. Unlike traditional analgesics, AS1892802 does not induce gastric irritation or abnormal behavior, making it a promising candidate for research in the treatment of severe osteoarthritis pain.

PF-4950834 is a potent, selective, and orally bioavailable ATP-competitive inhibitor of Rho-associated kinases, with IC₅₀ values of 8.35 nM for ROCK2 and 33.12 nM for ROCK1. It effectively inhibits neutrophil migration and is suitable for research on inflammation and immune cell regulation.

OXA-06 hydrochloride is an ATP-competitive inhibitor of Rho-associated protein kinase (ROCK) that suppresses anchorage-dependent growth and invasion of non-small cell lung cancer (NSCLC) cell lines. It inhibits cofilin phosphorylation without inducing apoptosis.

Hispidin is a phenolic compound and protein kinase C (PKC) inhibitor derived from *Phellinus linteus*. It exhibits strong antioxidant, anticancer, antidiabetic, and anti-dementia activities, making it a promising candidate for research in various disease models.

MY-673 is a colchicine binding site inhibitor (CBSI) that disrupts microtubule dynamics by inhibiting tubulin polymerization. In addition to its antimitotic effects, MY-673 suppresses the ERK signaling pathway, which leads to modulation of SMAD4 protein expression within the TGF-β/SMAD signaling axis. These combined actions result in potent inhibition of cancer cell proliferation and migration, and the induction of apoptosis, both in vitro and in vivo. MY-673 holds promise as a therapeutic candidate for targeting cancers driven by aberrant microtubule dynamics and dysregulated TGF-β/ERK signaling.

HA-1004 is a selective and multifunctional inhibitor of cyclic nucleotide-dependent protein kinases, including protein kinase A (PKA) and cyclic GMP-dependent protein kinase (PKG). It regulates key second messenger pathways involving cyclic AMP and cyclic GMP and has broad pharmacological effects. HA-1004 inhibits lipolysis and induces vascular smooth muscle relaxation, acting as a vasodilator. It also functions as a calcium antagonist, contributing to its ability to suppress contraction in rabbit aortic strips. In neurological models, HA-1004 has been shown to antagonize ERK and tyrosine hydroxylase (TH) phosphorylation in morphine abstinence rat models, suggesting potential relevance in addiction and neurochemical regulation. Its diverse actions make it a valuable tool for studying cardiovascular, metabolic, and neurobiological processes.

Akt1&PKA-IN-2 (Compound R-29) is a AKT1 and PKA inhibitor with selectivity for CDK2, with IC50 values of 0.007 and 0.01 μM, respectively. Akt1&PKA-IN-2 is applicable for cancer research.

Akt1&PKA-IN-1 is a potent dual inhibitor targeting both Akt and Protein Kinase A (PKA), exhibiting IC50 values of 0.03 μM for PKAα and 0.11 μM for Akt, with a higher IC50 of 9.8 μM for cyclin-dependent kinase 2 (CDK2). This compound demonstrates selective inhibition of CDK2, making it a valuable tool for research in cancer biology and cellular signaling pathways. Akt1&PKA-IN-1 is useful for studying the regulatory role of these kinases in cellular processes and potential therapeutic applications.

Netarsudil hydrochloride is a selective inhibitor of Rho-associated protein kinases (ROCK I and ROCK II) and a reversible inhibitor of the norepinephrine transporter (NET). It effectively lowers intraocular pressure by promoting relaxation of trabecular meshwork cells and dilation of episcleral veins, enhancing aqueous humor outflow while simultaneously reducing its production. This compound is primarily utilized in research related to ocular hypertension and primary open-angle glaucoma.

Metadoxine is a potent inhibitor of protein kinase A (PKA), specifically disrupting the PKA-cAMP response element binding protein (CREB) pathway. This compound is effective in blocking adipocyte differentiation, making it valuable for research into metabolic disorders and obesity-related pathways. Its ability to modulate PKA activity demonstrates potential applications in studying cellular signaling and metabolic regulation.

H-9 Dihydrochloride is a potent inhibitor of protein kinase A (PKA), effectively modulating signaling pathways involved in various biological functions. At a concentration of 10 μM, it significantly diminishes the excitatory response to 5-hydroxytryptamine (5-HT) and exhibits direct effects on pharyngeal activity. Additionally, H-9 Dihydrochloride inhibits signal transduction and cell growth in epidermal growth factor (EGF)-dependent epithelial cell lines, making it a valuable tool for research in cellular signaling and growth regulation.

NSC668394 is a selective inhibitor of ezrin phosphorylation at threonine 567, exhibiting a Kd of 12.59 μM. This compound effectively prevents the phosphorylation of ezrin induced by PKCΙ through direct binding, thereby interfering with key signaling pathways. NSC668394 is primarily utilized in research focused on inhibiting tumor metastasis and studying ezrin's role in cancer progression.

R59949 is a pan diacylglycerol kinase (DGK) inhibitor that exhibits an IC50 of 300 nM. This compound effectively inhibits the activity of type I DGK α and γ, while also moderately reducing the activity of type II DGK θ and κ. Additionally, R59949 promotes the activation of protein kinase C (PKC) by increasing endogenous diacylglycerol levels. It serves as a valuable tool for studying DGK and PKC signaling pathways in various biological contexts.

PKN1/2-IN-1 is a selective inhibitor of protein kinase N isoforms 1 and 2 (PKN1 and PKN2), demonstrating IC50 values of 16 nM and 210 nM, respectively, along with Ki values of 8 nM and 108 nM. This compound effectively permeates cell membranes and shows significant binding affinity for PKN2, as indicated by NanoBRET assays (IC50 = 2.1 μM). PKN1/2-IN-1 is valuable for investigating physiological processes, particularly in research focused on tumor cell migration and related signaling pathways.

CC-90005 is a potent and selective inhibitor of protein kinase C-θ (PKC-θ), exhibiting an IC50 of 8 nM. This compound demonstrates considerable selectivity for PKC-θ over PKC-δ, with an IC50 of 4440 nM. CC-90005 effectively inhibits T cell activation by downregulating IL-2 expression, making it a valuable tool for research in immunology and T cell signaling pathways.

ZIP is a selective peptide inhibitor of Protein Kinase M zeta (PKMζ), which plays a crucial role in synaptic plasticity and memory processes. This compound effectively impairs morphine-induced conditioned place preference, making it a valuable tool for studying addiction and the molecular mechanisms underlying memory formation. Research applications include investigating the role of PKMζ in memory reinforcement and the modulation of synaptic strength.

Procyanidin A1 is a potent inhibitor of protein kinase C (PKC) activity, effectively blocking degranulation processes in response to PKC activation and calcium influx in RBL-213 mast cells. This compound exhibits significant antiallergic properties, making it valuable for research applications focused on allergic responses and related signaling pathways. Its ability to modulate cellular activities makes Procyanidin A1 a useful tool in studying allergic mechanisms and developing therapeutic strategies.

N-Desmethyltamoxifen hydrochloride is a prominent inhibitor of protein kinase C (PKC). As the primary metabolite of tamoxifen, it exhibits ten-fold greater potency against PKC compared to its predecessor. Additionally, this compound effectively regulates ceramide metabolism in human acute myeloid leukemia (AML) cells by limiting ceramide glycosylation, hydrolysis, and sphingosine phosphorylation. Its properties make it valuable for research in cancer biology and metabolic regulation.

H-7 dihydrochloride is a potent inhibitor of protein kinase C (PKC), effectively blocking its activity. At a concentration of 100 μM, H-7 dihydrochloride completely inhibits ornithine decarboxylase induction stimulated by both TPA (12-O-tetradecanoylphorbol-13-acetate) and phospholipase C. This reagent is widely utilized in research to investigate PKC-related signaling pathways and its role in cellular processes such as proliferation and differentiation.

Cercosporin is a potent protein kinase C (PKC) inhibitor derived from the plant pathogen Pseudocercosporella capsellae. This compound acts as an effective photosensitizer due to its short activation wavelength, making it particularly suitable for superficial photodynamic therapy (PDT) applications where avoiding tissue perforation is crucial. With an IC50 ranging from 0.6 to 1.3 μM, cercosporin showcases significant biological activity in modulating cellular signaling pathways, contributing to its potential utility in cancer research and therapeutic development.

Aurothiomalate sodium is a selective inhibitor of the oncogenic protein kinase C iota (PKCι), demonstrating significant potential in cancer research. This compound effectively inhibits tumor cell proliferation while having minimal effects on cell apoptosis, highlighting its unique mechanism of action. Additionally, Aurothiomalate sodium acts as a potent inhibitor of thioredoxin reductase (TrxR) and possesses anti-tumor properties, making it a valuable tool for investigating signaling pathways involved in cancer biology and therapeutic responses. Its anti-rheumatic properties further extend its relevance in related biomedical studies.

PS432 is a selective protein kinase C (PKC) inhibitor, demonstrating IC50 values of 16.9 μM for PKCι and 18.5 μM for PKCζ. This compound effectively reduces the proliferation of non-small cell lung cancer (NSCLC) cells and inhibits tumor growth in mouse xenograft models. It serves as a valuable tool for research applications targeting PKC signaling pathways in cancer biology.

Protein kinase inhibitor H-7 is a selective inhibitor of protein kinase C (PKC) and cyclic nucleotide-dependent protein kinase, exhibiting a Ki of 6 μM for PKC. This compound has been widely used in research to investigate the role of PKC in various cellular processes, including signal transduction and cell proliferation. Additionally, H-7 serves as a valuable tool in studies focused on the modulation of kinases and their associated pathways.

Aprinocarsen sodium is a specific antisense oligonucleotide that targets protein kinase C-alpha (PKC-α), functioning as a potent inhibitor. This 20-mer oligonucleotide modulates cellular processes such as differentiation and proliferation. In vivo studies demonstrate its ability to inhibit the growth of human tumor cell lines in nude mice, highlighting its potential utility as a chemotherapeutic agent in the treatment of various human cancers.

Bisindolylmaleimide II is a potent inhibitor of Protein Kinase C (PKC) isoforms, serving as a valuable tool for dissecting PKC-related signaling pathways. Its inhibitory effect on all PKC subtypes makes it useful in studies investigating cellular processes such as proliferation, differentiation, and apoptosis. This compound is widely applied in research aiming to elucidate the role of PKC in various disease models, including cancer and neurodegenerative disorders.

SBI-0087702 is a selective inhibitor of ATF2, primarily targeting its phosphorylation at Thr52 by PKCε. This reagent induces the translocation of ATF2 to the mitochondria in melanoma cells, leading to enhanced apoptosis through the disruption of mitochondrial membrane integrity. Additionally, SBI-0087702 demonstrates significant effects on reducing both the growth and motility of melanoma cells, making it a valuable compound for research into cancer biology and therapeutic applications.

Bacopaside I is a selective AQP1 inhibitor and protein kinase C (PKC) modulator with notable neuroprotective and anticancer properties. It specifically inhibits the water channel and cGMP-gated ion channel activities of AQP1, thereby reducing the migration of AQP1-expressing colon cancer cells. Additionally, Bacopaside I activates the Akt pathway through PI3K interaction, inhibits MAO-A, and mitigates neuron necrosis and apoptosis due to oxygen-glucose deprivation, while lowering oxidative stress and modulating neuroreceptor expression. This compound is relevant for research in colon cancer, breast cancer, vascular dementia, cerebral ischemia, and associated diseases.

Protein Kinase Inhibitor 9 is a potent inhibitor of serine/threonine and tyrosine kinase activity. It demonstrates significant anti-proliferative effects, making it valuable for cancer research and the study of hyperproliferative disorders. Additionally, this compound can be applied in investigations related to rheumatoid arthritis, immune system dysfunctions, transplant rejections, and inflammatory disorders.

Bisindolylmaleimide III is a selective inhibitor of protein kinase C alpha (PKCα), effectively disrupting its activity. This compound selectively engages with PKCα or ribosomal S6 protein kinase 1 following their activation, making it a valuable tool in dissecting PKC-related signaling pathways. It is widely utilized in cancer research and studies investigating cell growth and differentiation.

PKCTheta-IN-2 is a highly potent and selective inhibitor of protein kinase C theta (PKCθ) with an IC50 value of 0.25 nM. This compound demonstrates exceptional selectivity for PKCθ over more than 30 other kinases within the PKC subfamily. PKCTheta-IN-2 effectively inhibits interleukin-2 (IL-2) production in murine models, exhibiting an IC50 of 682 nM. Its use in research is particularly relevant for studies involving T cell signaling and autoimmune disorders.

Sphingosine (d14:1), also known as Tetradecasphing-4-enine, is a selective inhibitor of Protein Kinase C (PKC). This sphingolipid disrupts the interaction between PKC and sn-1,2-diacylglycerol (DAG) or phorbol esters, thereby modulating signaling pathways. Sphingosine (d14:1) is primarily utilized in research investigating cellular processes regulated by PKC, including cell proliferation, differentiation, and apoptosis.

Bisindolylmaleimide XI hydrochloride is a potent and selective inhibitor of protein kinase C (PKC) with IC50 values of 9 nM, 28 nM, 31 nM, 37 nM, and 108 nM for PKCα, PKCβI, PKCβII, PKCγ, and PKCε, respectively. This compound is orally active, making it a valuable tool for exploring the role of PKC in various cell signaling pathways. Its application spans cancer research, neurobiology, and cardiovascular studies, providing insights into PKC-mediated processes and potential therapeutic targets.

(Rac)-Anemonin is a dual inhibitor targeting inducible nitric oxide synthase (iNOS) and protein kinase C theta (PKC-θ). It selectively inhibits iNOS while also reducing the stability of the PKC-θ protein, showcasing significant biological activity. Research indicates that (Rac)-Anemonin can alleviate symptoms in dextran sodium sulfate-induced acute ulcerative colitis in murine models, making it valuable for studying inflammation-related diseases.

Ruboxistaurin mesylate is a selective and ATP-competitive inhibitor of protein kinase C-beta (PKCβ) with IC50 values of 4.7 nM and 5.9 nM for the PKCβI and PKCβII isoforms, respectively. This compound shows potential in the study of several pathological conditions, including eye disorders, heart failure, and diabetes. Its specific inhibition of PKCβ can facilitate investigations into the underlying mechanisms of these diseases and the development of targeted therapeutic strategies.

N-Desmethyltamoxifen, a potent protein kinase C (PKC) inhibitor, is the primary metabolite of tamoxifen in humans. It demonstrates significantly enhanced PKC inhibitory activity, being ten-fold more potent than its precursor. Additionally, N-Desmethyltamoxifen effectively regulates ceramide metabolism in human acute myeloid leukemia (AML) cells, influencing ceramide glycosylation, hydrolysis, and sphingosine phosphorylation, making it a valuable tool for cancer research and therapeutic studies.

SAMβA is a selective inhibitor targeting the interaction between mitofusin 1 and βIIPKC. This compound is conjugated to the cell-permeable peptide TAT47-57, facilitating its penetration into cells. SAMβA has demonstrated potential in enhancing heart failure outcomes in rat models, making it a valuable tool for investigating mitochondrial dynamics and associated pathophysiological processes in cardiac research.

NPC-15437 dihydrochloride is a selective and reversible inhibitor of protein kinase C (PKC), demonstrating an IC50 value of 19 μM. This compound has been shown to impact the mechanisms associated with memory consolidation, making it a valuable tool for studying cognitive processes and neurobiology. Its penetrative properties enable effective investigation in various biological systems.

(S)-Ro 32-0432 is a selective, orally active inhibitor of protein kinase C (PKC), exhibiting ATP-competitive properties. Its IC50 values demonstrate high potency against various PKC isoforms, including PKCα (9.3 nM) and PKCβI (28 nM). Additionally, (S)-Ro 32-0432 acts as an inhibitor of G protein-coupled receptor kinase 5 (GRK5). This compound is valuable for investigating T-cell activation mechanisms and is relevant for research in chronic inflammatory and autoimmune diseases.

N-myristoyl-RKRTLRRL is a potent inhibitor of Protein Kinase C (PKC), specifically targeting the binding of PKC substrates. This compound effectively inhibits calcium- and phosphatidylserine-dependent histone phosphorylation, demonstrating an IC50 of 5 µM. It serves as a valuable tool for research into PKC-related signaling pathways and the mechanisms of histone modification in various biological contexts.