Protein Kinase A (PKA)

PKA Substrate is a selective peptide designed for the measurement of protein kinase A (PKA) activity. This substrate undergoes phosphorylation in the presence of active PKA, allowing for the detection and quantification of kinase activity in various biological samples. Its utility in biochemical assays makes it an essential tool for researchers investigating PKA-mediated signaling pathways.

GSK466317A is a potent protein kinase A (PKA) inhibitor, exhibiting an IC50 of 12.59 μM. In addition to its primary target, GSK466317A also demonstrates inhibitory activity against GRK1, GRK2, and GRK5, with corresponding IC50 values of 1000 μM, 31.62 μM, and 39.81 μM, respectively. This compound is valuable for research applications involving signal transduction pathways and the study of G protein-coupled receptor (GPCR) functionality.

Protein Kinase Inhibitor 7 is an inhibitor of Protein Kinase A (PKA) and Protein Kinase C (PKC). This compound modulates the autocrine motility factor (AMF) signaling pathway, demonstrating potential applications in cancer research and studies involving cell signaling without influencing overall cell motility. It is a valuable tool for elucidating the roles of PKA and PKC in various biological processes.

ME 3407 is a myosin light chain kinase (MLCK) and protein kinase A (PKA) inhibitor that disrupts H+-K+-ATPase redistribution. This compound effectively blocks gastric acid secretion and inhibits aminopyrine accumulation by preventing the microsomal-to-apical membrane redistribution of H+-K+-ATPase. ME 3407 demonstrates potential for use in research related to peptic ulcers and other gastrointestinal disorders.

Sp-cAMPS-AM is a cell-permeable analog of cyclic AMP (cAMP) that functions as a potent activator of Protein Kinase A (PKA). Upon cellular uptake, it releases its parent compound, Sp-cAMPS, which subsequently promotes PKA activation and CREB phosphorylation. This reagent is valuable for research applications in signaling pathways involving cAMP and PKA, facilitating studies on gene expression and cellular response mechanisms.

Sp-8-pCPT-cGMPS is a potent activator of protein kinase G (PKG) and protein kinase A (PKA) with significant cell membrane permeability and phosphodiesterase stability. This cyclic guanosine monophosphate analog effectively engages PKG types I α, I β, and II, making it invaluable for research in signal transduction pathways. It is utilized to investigate the role of cGMP in neural plasticity, synaptic transmission, and other physiological processes influenced by these kinases.

FMP-API-1 is an inhibitor of the A-kinase anchoring protein (AKAP)-PKA interaction. By binding to the allosteric site of protein kinase A (PKA) regulatory subunits, FMP-API-1 enhances PKA activity and promotes the function of aquaporin-2 (AQP2) in PKA-knockout renal cortical collecting duct cell lines (mpkCCD cells). This compound is valuable for investigating nephrogenic diabetes insipidus (NDI) and the underlying mechanisms of renal water transport.

8-MA-cAMP (8-Methylamino-cAMP) is a cyclic AMP analog that serves as a selective agonist for protein kinase A (PKA), specifically targeting the B site of both type I and type II PKA. This compound demonstrates key biological activity by effectively modulating PKA-mediated signaling pathways. Researchers utilize 8-MA-cAMP in combination with priming analogs, such as 8-piperidinyl cAMP, to achieve precise activation of type I PKA, making it valuable for studies in cellular signaling and related therapeutic research.

Sp-6-Phe-cAMPS is a potent, selective activator of cAMP-dependent protein kinase (PKA) that exhibits membrane permeability. This compound uniquely does not directly activate exchange factors that are normally stimulated by cAMP, serving as a useful negative control for Epac studies. Sp-6-Phe-cAMPS is valuable in research focusing on neurodegenerative diseases, facilitating investigations into PKA signaling pathways and their implications in these conditions.

6-Bn-cAMP is a potent site-selective activator of cAMP-dependent protein kinase (PKA), specifically designed not to activate Epac. This compound demonstrates enhanced hydrolytic stability against phosphodiesterases, esterases, and amidases, along with significantly improved membrane permeability compared to standard cAMP. It is widely utilized in research applications aimed at elucidating PKA signaling pathways and their biological implications.

6-Phe-cAMP is a potent and membrane-permeant activator of protein kinase A (PKA), specifically targeting site A of both PKA isozymes. This compound demonstrates strong selectivity, making it an invaluable tool for studying PKA-mediated signaling pathways. Additionally, 6-Phe-cAMP is amenable to phosphorothioate modification, facilitating further research applications in cellular and molecular biology.

Balanol is a highly selective ATP-competitive inhibitor of Protein Kinase C (PKC) and Protein Kinase A (PKA), demonstrating potent activity against various human PKC isozymes, including α, β-I, β-II, γ, δ, ε, η, and ζ, with IC50 values ranging from 4 to 150 nM. This compound effectively inhibits the phosphorylation of key downstream targets such as cyclic AMP response element-binding protein (CREB) and myristoylated alanine-rich C kinase substrate (MARCKS). Balanol can be isolated from the fungus Verticillium balanoides, making it a valuable tool for research involving PKC/PKA signaling pathways.

PKA/AKAP-IN-2 is a non-peptide inhibitor targeting the interaction between protein kinase A (PKA) and A kinase anchoring proteins (AKAP). This compound disrupts the PKA-AKAP binding, providing valuable insights into signaling pathways influenced by cAMP. PKA/AKAP-IN-2 is useful for research into diseases linked to cAMP dysregulation and the broader implications of PKA signaling in cellular processes.

4-Cyano-3-methylisoquinoline is a potent protein kinase A (PKA) inhibitor, exhibiting an IC50 at the micromolar range. This compound has demonstrated the ability to reverse morphine tolerance in murine models, highlighting its potential use in pain management research and studies exploring opioid signaling pathways. Its role as a PKA inhibitor makes it a valuable tool for investigating cellular processes regulated by this important kinase.

PKA/AKAP-IN-1 is a potent non-peptide inhibitor that selectively disrupts the interaction between protein kinase A (PKA) and A-kinase anchoring proteins (AKAP). This compound is valuable for investigating the role of cAMP signaling in various pathological conditions associated with its dysregulation. Research applications include studies on cellular signaling pathways and potential therapeutic interventions in diseases linked to altered PKA/AKAP interactions.

8-OH-cAMP (8-Hydroxy-cAMP) is a polar, membrane-impermeable analog of cyclic adenosine monophosphate (cAMP) that selectively activates protein kinase A (PKA) while resisting degradation by cyclic nucleotide-dependent phosphodiesterases. This compound serves as a valuable tool for investigating the role of cAMP signaling in various biological processes, particularly in cardiovascular and metabolic disease research. Its unique properties enable researchers to elucidate PKA-mediated pathways and their implications in disease development.

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.

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.

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.

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.

MK2-IN-1 hydrochloride is a potent and selecitve MAPKAPK2(MK2) inhibitor(IC50=0.11 uM) with a non-ATP competitive binding mode.

HA-100 is an isoquinoline compound with an added piperazinylsulfonyl group that acts as an inhibitor of protein kinases (PKs), including PKA, PKC, and PKG (IC50s = 8, 12, and 4 ?M, respectively).

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.

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.

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.

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.

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.

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.

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.

st-Ht31 is a membrane-permeable peptide that inhibits protein kinase A (PKA) anchoring. It effectively induces cholesterol and phospholipid efflux and has been shown to completely reverse foam cell formation in macrophages. This compound offers valuable insights into PKA-related signaling pathways and metabolic health research.

2'-Deoxy-NAD+ sodium is a sodium salt derivative of 2'-Deoxy-NAD+ that functions as a noncompetitive inhibitor of NAD+ with a Ki value of 32 μM. This reagent is valuable for investigating ADP-ribosyl transfer reactions, providing insights into cellular processes involving protein modification. It is particularly useful in studies related to protein kinase A (PKA) activity and regulatory mechanisms in biological systems.

Phosphate acceptor peptide is a specific substrate for cyclic AMP-dependent protein kinase (PKA), facilitating the study of phosphorylation processes. Additionally, it exhibits weak inhibitory activity against protein kinase C (PKC), making it useful in exploring the mechanisms of kinase signaling pathways. This reagent is applicable in various biochemical assays aimed at understanding cellular signaling and regulation.