TGF-β/Smad

Sp-8-Br-cAMPS is a synthetic analog of cyclic adenosine monophosphate (cAMP) and serves as a potent agonist for protein kinase A (PKA) with an EC50 of 360 nM. This compound effectively activates PKA and has been shown to inhibit T cell proliferation and modulate the hemocyte non-self response in Lepidoptera larvae. Its significant biological activity makes it a valuable tool for research into PKA-mediated signaling pathways and immune responses.

ROCK2-IN-12 is a selective ROCK2 inhibitor, demonstrating an IC50 of 7.0 nM for ROCK2 relative to ROCK1. This compound exhibits potent antifibrotic effects by modulating the TGF-β/Smad and ROCK2/STAT3 signaling pathways, effectively reducing collagen deposition and reversing fibrosis in Bleomycin-induced pulmonary fibrosis mouse models. ROCK2-IN-12 is suitable for investigating lung diseases, particularly pulmonary fibrosis.

ROCK2-IN-7 is a selective inhibitor of the Rho-associated protein kinase 2 (ROCK2). It effectively disrupts ROCK2/pSTAT3 signaling pathways, leading to decreased systemic immune activation and reduced inflammation. This compound is particularly valuable in studies related to autoimmune conditions, such as psoriasis, as it provides insights into the modulation of immune responses and inflammatory processes.

8-Benzylthio-cAMP is a selective activator of cAMP-dependent protein kinases (PKA) that serves as a stable derivative of cyclic adenosine monophosphate (cAMP). Its increased resistance to phosphodiesterase hydrolysis and enhanced membrane permeability make it an effective tool for probing cAMP signaling pathways. This compound is widely used in research to investigate the regulatory roles of cAMP in cellular processes such as proliferation, differentiation, and apoptosis.

(14S,15R)-14-Deoxyoxacyclododecindione is a selective inhibitor of the TGF-β-dependent Smad2/3 and IL-4-dependent STAT6 signaling pathways, exhibiting IC50 values of 90 nM and 20 nM, respectively. This compound has significant potential for applications in cancer research and the study of fibrotic diseases by modulating key signaling events. Its ability to inhibit these pathways makes it a valuable tool for investigating the role of TGF-β and IL-4 in various biological processes.

Akt/ROCK-IN-1 is a potent dual inhibitor targeting Akt and ROCK, exhibiting IC50 values of 0.023 nM and 1.47 nM, respectively. This compound demonstrates significant antitumor activity, particularly in neuroblastoma models. It serves as a valuable tool for research into cancer biology and therapeutic development.

TGF-βRI inhibitor 3 is a selective inhibitor of the TGF-β receptor type I (ALK5), designed to effectively disrupt TGF-β signaling pathways. It demonstrates notable inhibitory activity with IC50 values of 0.63 μM against ALK5 and 13 μM against c-Src kinase. This compound is valuable for research applications targeting fibrosis, cancer progression, and other TGF-β-mediated biological processes.

RepSox hydrochloride is a highly selective inhibitor of transforming growth factor-β receptor I (TGF-β-RI) and activin-like kinase 5 (ALK5). It effectively inhibits ALK5 autophosphorylation with an IC50 value of 4 nM. This reagent is valuable for investigating the roles of TGF-β signaling in obesity and metabolic disorders, including type 2 diabetes.

MK2-IN-1 is a selective inhibitor of MAPKAPK2 (MK2), exhibiting an IC50 of 0.11 µM. This compound significantly interferes with the phosphorylation of serine residues in Tfcp2l1, with an EC50 of 0.35 µM for phosphorylated HSP27. MK2-IN-1 serves as a valuable tool for studying the role of MK2 in cellular signaling pathways and its implications in various biological processes.

Bryostatin 1 is a macrolactone isolated from the marine bryozoan, Bugula neritina, that modulates protein kinase C (PKC) activity. Bryostain 1 induces an initial rapid activation and autophosphorylation of PKC that results in the translocation of the PKC enzyme to the membrane.

Daphnetin is a coumarin analog that acts as an inhibitor of several protein kinases. It inhibits EGFR kinase (IC50 = 7.67 μM), PKA (IC50 = 9.33 μM), and PKC (IC50 = 25 μM), in vitro. The inhibition of EGFR kinase by daphnetin was competitive to ATP and non-competitive to the peptide substrate. Also acts as a potent antioxidant and anti-malarial agent.

GSK429286A is a cell-permeable, selective small molecule inhibitor of Rho-associated, coiled-coil containing protein kinase (ROCK).

Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, ?€?Chen Pi.?€? Hesperetin is a citrus flavonoid that has been reported to lower plasma cholesterol. Hesperetin reduces the transcription of ACAT-2 mRNA in Hep-G2 cells and reduces ApoB protein synthesis in a dose-dependent manner. It also is a potential therapy for carcinoid cancer.

SB525334 is a selective inhibitor of transforming growth factor-β receptor I (ALK5, TGF-βRI) (IC50 = 14.3 nM). Inhibits TGF-β1-induced smad2/3 nuclear localization and TGF-βRI-induced mRNA expression in kidney cells

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).

Malantide is a synthetic dodecapeptide derived from the site phosphorylated by cAMP-dependent protein kinase (PKA) on the β-subunit of phosphorylase kinase. Malantide is a highly specific substrate for PKA with a Km of 15 μM and shows protein inhibitor (PKI) inhibition >90% substrate phosphorylation in various rat tissue extracts. Malantide is also an efficient substrate for PKC with a Km of 16 μM.

Protein Kinase C (19-31), a peptide inhibitor of protein kinase C (PKC), derived from the pseudo-substrate regulatory domain of PKCa (residues 19-31) with a serine at position 25 replacing the wild-type alanine, is used as protein kinase C substrate peptide for testing the protein kinase C activity. Protein kinase C (PKC) is involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins.

(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine functions as a dual-target PROTAC, effectively inducing ubiquitination and degradation of Smad3 while simultaneously enhancing HIF-α protein levels. This compound exhibits multi-pathway anti-fibrotic activity and renal protective properties, making it valuable for research on renal anemia. Additionally, it has potential applications in studying prostate cancer and other malignancies, contributing to a deeper understanding of cancer biology and treatment modalities.

Bilobetin acts as a PPARα activator, enhancing lipid metabolism and insulin sensitivity. It effectively reduces blood lipid levels by promoting hepatic lipid uptake and oxidation, while decreasing triglyceride secretion and accumulation in tissues. Additionally, Bilobetin stimulates the phosphorylation and nuclear translocation of PPARα, resulting in increased cAMP levels and PKA activity. This compound is significant for research in metabolic disorders, particularly those related to insulin resistance and lipid regulation.

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.

8-Bromo-cAMP, a cyclic AMP analog, serves as a potent activator of cyclic AMP-dependent protein kinase (PKA). This compound demonstrates significant anti-proliferative and apoptotic effects in various cancer cell lines, making it a valuable tool for cancer research. Its role in modulating PKA activity provides insights into cellular signaling pathways and the mechanisms of tumorigenesis. 8-Bromo-cAMP is commonly utilized in studies aimed at understanding the therapeutic potential of targeting PKA in cancer treatment.

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.

IDE2 is a cell-permeable small molecule that promotes definitive endoderm formation in both mouse and human embryonic stem cells (ESCs) through activation of the TGF-β signaling pathway.

Lobeglitazone sulfate is a novel thiazolidinedione and an orally active agonist of peroxisome proliferator-activated receptors (PPARs), with EC50 values of 137.4 nM for PPARγ and 546.3 nM for PPARα. It also acts as an inhibitor of the ERK/JNK/Smad/NF-κB signaling pathways. Lobeglitazone sulfate exhibits anti-inflammatory, anti-diabetic, anti-fibrotic, and anti-atherosclerotic activities, supporting its potential in the treatment of metabolic and inflammatory diseases.

Gardenin A is an orally active synthetic polymethoxyflavone (PMF) analogue with neurotrophic properties, promoting neurite outgrowth and neuronal differentiation. It enhances neuritogenesis through activation of the MAPK/ERK, PKC, and PKA pathways, independent of TrkA and CREB signaling. Additionally, Gardenin A exhibits sedative, anxiolytic, antidepressant, and anticonvulsant effects, making it a promising compound for neurological and neuropsychiatric research.

Gondoic acid (cis-11-Eicosenoic acid) is a monounsaturated long-chain fatty acid found in various plant oils and nuts. It exhibits anti-inflammatory activity by reducing reactive oxygen species (ROS) production and inhibiting the PKCθ/ERK/STAT3 signaling pathway. Gondoic acid is also utilized as a raw material in medical applications and as a moisturizing agent in cosmetic formulations.

Lobeglitazone is a novel thiazolidinedione-class compound and an orally active dual agonist of peroxisome proliferator-activated receptors (PPARs), with EC₅₀ values of 137.4 nM for PPARγ and 546.3 nM for PPARα. In addition to its metabolic effects, Lobeglitazone functions as an inhibitor of multiple pro-inflammatory and pro-fibrotic signaling pathways, including ERK, JNK, Smad, and NF-κB. Lobeglitazone exhibits a broad range of pharmacological activities, including anti-inflammatory, anti-diabetic, anti-fibrotic, and anti-atherosclerotic effects. These properties make it a promising candidate for therapeutic research in metabolic syndrome, type 2 diabetes, cardiovascular disease, and fibrosis-related conditions.

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.

4′-Demethylnobiletin is a bioactive metabolite derived from citrus polymethoxyflavones, known for its neuroprotective and cognition-enhancing properties. It activates the PKA/ERK/CREB signaling pathway and enhances CRE (cAMP response element)-mediated transcription in hippocampal neurons, processes essential for synaptic plasticity and memory formation. Additionally, 4′-Demethylnobiletin reverses memory impairment caused by NMDA receptor antagonism by stimulating ERK signaling, highlighting its therapeutic potential for neurodegenerative diseases and cognitive dysfunction.

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.

ML192 is a selective antagonist of G protein-coupled receptor 55 (GPR55), effectively inhibiting GPR55-mediated signaling pathways. It blocks β-arrestin trafficking, suppresses ERK1/2 phosphorylation, and prevents PKCβII translocation, thereby interfering with downstream cellular responses. ML192 is a valuable tool for studying the physiological and pathological roles of GPR55 in processes such as inflammation, pain, cancer, and metabolic regulation.

SY-LB-35 is a potent agonist of bone morphogenetic protein (BMP) receptors, capable of activating both canonical and non-canonical signaling pathways. In the C2C12 myoblast cell line, SY-LB-35 significantly enhances cell proliferation and viability, promoting cell cycle progression by increasing the proportion of cells in the S and G2/M phases. Mechanistically, it activates the canonical Smad pathway as well as non-canonical PI3K/Akt, ERK, p38, and JNK signaling cascades. These properties make SY-LB-35 a valuable tool for studying BMP-related cellular processes and a potential therapeutic candidate for tissue regeneration and muscle repair.

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.