pka-in-1

PKA-IN-1 is a selective and potent cyclic AMP-dependent protein kinase (PKA) catalytic subunit (cAK) inhibitor (IC50: 0.03 μM).PKA-IN-1 can be used to study diseases of the immune system.

Akt1&PKA-IN-1 is a potent dual inhibitor targeting Akt and PKA, exhibiting IC50 values of 0.11 μM for Akt, 0.03 μM for PKAα, and 9.8 μM for CDK2. Notably, it demonstrates selectivity for cyclin-dependent kinase 2 (CDK2).

A-674563 is an orally available, ATP-competitive, and reversible inhibitor of Akt (Ki: 11 nM for Akt1) [1]. It exhibits inhibitory activity against PKA and Cdk2 (IC50: 16/46 nM) but is 10- to >1, 800-fold selective for Akt1 versus additional kinases in th

4′-Demethylnobiletin, a bioactive metabolite, activates the PKA/ERK/CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and reverses memory impairment linked to NMDA receptor antagonism through ERK signaling stimulation [1].

Urocortin II, mouse, is a selective and potent endogenous peptide agonist for the type-2 corticotropin-releasing factor (CRF2) receptor, displaying K_i values of 0.66 nM for CRFR2 and >100 nM for CRFR1, signifying its high specificity. It engages CRF2 receptors through mechanisms dependent on cAMP/PKA and Ca2+/CaMKII. Additionally, Urocortin II, mouse is localized in specific regions of the central nervous system, influencing central neurons that process visceral sensory information and regulate autonomic functions [1] [2] [3].

st-Ht31, a cell-permeable stearated peptide derived from the amphipathic helix domain of A-kinase anchoring proteins (AKAPs), effectively binds protein kinase A (PKA), impacting PKA's cellular interactions without altering its activity. Specifically, at a 50 µM concentration, it reduces PKA's membrane anchoring in BHK-21 fibroblast reporter assays. Moreover, st-Ht31 at concentrations of 1 and 3 µM decreases both capacitance and hyperactivation in mouse sperm, thereby inhibiting in vitro fertilization. Additionally, at 50 µM, this compound facilitates cholesterol export in BHK-21 cells and RAW 264.7 macrophages expressing ATP-binding cassette transporter 1 (ABCA1), showcasing its multifaceted cellular impacts.

CL4F8-6, an ionizable cationic lipid with a pKa of 6.14, is utilized in lipid nanoparticles (LNPs) for mRNA therapeutics. When incorporated into LNPs delivering Cas9 mRNA and sgRNA, CL4F8-6 facilitates CRISPR-mediated gene knockdown in mice [1].

Malantide TFA, a synthetic dodecapeptide, originates from the phosphorylation site targeted by cAMP-dependent protein kinase (PKA) on the β-subunit of phosphorylase kinase. Exhibiting a high specificity for PKA with a Michaelis constant (Km) of 15 μM, this compound demonstrates more than 90% inhibition of substrate phosphorylation in the presence of protein inhibitor (PKI) across various rat tissue extracts [1]. Moreover, Malantide TFA acts as an effective substrate for Protein Kinase C (PKC) with a Km of 16 μM [2].

H1-7 (histone H1 phosphorylation site), a synthetic polypeptide serving as a PKA substrate, demonstrates utility in PKA substrate applications [1] [2].

SB-747651A is a potent, ATP-competitive inhibitor of mitogen- and stress-activated kinase 1 (MSK1, IC50 = 11 nM). It targets the N-terminal kinase domain. SB-747651A inhibits MSK1, MSK2, PKA, PKB, RSK and p70S6K activity in cells.

PKI (14-24)amide is a potent inhibitor of Protein Kinase A (PKA), demonstrating strong inhibition of cyclic AMP-dependent protein kinase activity in cell homogenates [1] [2].

PKC412(Midostaurin (PKC412); CGP41231; CGP41251) is a broad spectrum protein kinase inhibitor. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.

API-1 (NSC-177223) is a potent inhibitor of Akt. It induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis .

Paraxanthine (1,7-dimethylxanthine) is a metabolite of caffeine (sc-202514) which functions as an adenosine receptor ligand and a PARP-1 inhibitor in pulmonary epithelial cells. Studies suggest that Paraxanthine is structurally similar to caffeine and possibly mediates the physiological effects of caffeine. Also Paraxanthine acts as a competitive phosphodiesterase inhibitor, which increases intracellular cAMP, activates PKA, inhibits TNF-α and leukotriene synthesis. In addition, Paraxanthine acts as a Na+/K+ ATPase enzymatic effector.

PKI(5-24) TFA is a synthetic peptide inhibitor of PKA (cAMP-dependent protein kinase), characterized by its potent and competitive inhibition properties, exhibiting a K i of 2.3 nM. It corresponds to residues 5-24 found in the natural heat-stable protein kinase inhibitor [1] [2].

1. Nardosinone has inhibitory effect on Ang II-induced hypertrophy in H9c2 cells, might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways. 2. Nardosinone could protect against the neuronal injury exposed to OGD, which may be relevant to the

Rp-cAMPS sodium salt, a cAMP analog, is a potent, competitive cAMP-induced activation of cAMP-dependent PKA I and II (Kis of 12.5 μM and 4.5 μM, respectively) antagonist. Rp-cAMPS sodium salt is resistant to hydrolysis by phosphodiesterases[1][2][3][4][5][6]. A membrane-permeable competitive cAMP antagonist (Rp-cAMPS) that blocks PKA activation by binding to the regulatory subunits without dissociating the kinase holoenzyme also inhibits synaptic plasticity but has no effect on normal synaptic transmission[2]. Rp-cAMPS (10 μM, 15 min) decreases the monosynaptic EPSCs evoked at the PB-CeLC and BLA-CeLC synapses in slices from arthritic rats but not in control neurons from normal animals. The inhibitory effect of Rp-cAMPS is significant compared to predrug (ACSF) control values obtained in the same neurons[2]. [1]. R J de Wit, et al. Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases. Eur J Biochem. 1984 Jul 16;142(2):255-60. [2]. Rothermel JD, et al. A mechanistic and kinetic analysis of the interactions of the diastereoisomers of adenosine 3’,5’-(cyclic)phosphorothioate with purified cyclic AMP-dependent protein kinase. Biochem J. 1988 May 1;251(3):757-62.[3]. Fu Y, et al. PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior. Mol Pain. 2008 Jul 16;4:26.[4]. Kuriyama S, et al. Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):730-6.[5]. Dostmann WR, et al. Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3’,5’-cyclic phosphorothioates. J Biol Chem. 1990 Jun 25;265(18):10484-91.[6]. Van Haastert PJ, et al. Competitive cAMP antagonists for cAMP-receptor proteins. J Biol Chem. 1984 Aug 25;259(16):10020-4.

BBT enhances glucose-stimulated insulin secretion (GSIS) in compromised conditions, demonstrates anti-hyperglycemia effects, and shields β-cells from cytokine- or streptozotocin (STZ)-triggered apoptosis in type 2 diabetes models. Its mechanism of action involves the cAMP/PKA and long-lasting (L-type) voltage-dependent Ca2+ channel/CaMK2 pathways [1].

1. 8-Gingerol has antioxidant activity. 2. 8-Gingerol has antimycobacterial activity. 3. 8-Gingerol could be used as an effective skin-whitening agent. 4. 8-Gingerol shows antipyretic and anti-inflammation characteristics. 5. 8-Gingerol seems to be effect

8-CPT-2Me-cAMP sodium is a sodium salt compound that selectively activates exchange proteins activated by cAMP (Epac). These Epac proteins are cAMP-sensitive guanine nucleotide exchange factors (GEFs) responsible for activating small GTPases Rap1 and Rap2. 8-CPT-2Me-cAMP sodium specifically activates Epac1 with an EC50 value of 2.2 μM, while showing no activation of PKA with an EC50 value greater than 10 μM [1]. Additionally, 8-CPT-2Me-cAMP sodium stimulates the Epac-mediated release of calcium ions (Ca2+) in vitro in pancreatic β-cells [2].

Tat-AKAP79 (326-336) is a peptide that links the HIV-1 Tat protein transduction domain with an 11-amino acid sequence from A-kinase anchor protein 79 (AKAP79). This compound effectively inhibits the activation-induced sensitization by protein kinase A (PKA) or PKC of the transient receptor potential vanilloid 1 (TRPV1) at a concentration of 200 µM in isolated rat dorsal root ganglion (DRG) neurons. Additionally, it mitigates nocifensive behavior in mice elicited by formalin or phorbol 12-myristate 13-acetate (PMA014), enhances latency for paw withdrawal from radiant heat, and raises the mechanical threshold force required for paw withdrawal in a carrageenan-induced mouse model of inflammatory pain.

Lipid AX4, characterized as an ionizable cationic lipid with a pKa of 6.89, facilitates the formation of lipid nanoparticles (LNPs) for in vivo mRNA delivery [1].

PIM1-IN-4 (Compound 8) is a potent PIM1 inhibitor with significant inhibitory activity against five additional enzymes: SGK-1, PKA, CaMK-1, GSK3β, and MSK1, rendering it a potentially useful agent for cancer research [1].

1. Fargesin ((+/-)-Fargesin) as a potential β1AR antagonist through cAMP/PKA pathway could protect against myocardial ischemia/reperfusion injury in rats. 2. Fargesin improves dyslipidemia and hyperglycemia by activating Akt and AMPK in WAT.