camp-signaling

Roflumilast (APTA 2217) is an orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3', 5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling.

ethyl 1-(4-aminophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate, also known as EAPT, is a potent and selective PDE4 inhibitor that regulates intracellular cyclic adenosine monophosphate (cAMP) levels. It has been used in a variety of scientific applications, including the study of cAMP-mediated signaling pathways, and has potential as a therapeutic agent for the treatment of inflammatory and immune-related diseases.

INT-777 (S-EMCA) is a potent TGR5 agonist with an EC50 of 0.82 μM. INT-777 (S-EMCA) inhibits NLRP5-ASC inflammasome-mediated neuroinflammation via the TGR3 cAMP PKA signaling pathway after subarachnoid hemorrhage in rats.

Polygalasaponin F has anti-neuroinflammatory activity, can inhibit the release of inflammatory cytokines TNF-α and NO induced by lipopolysaccharides (LPS) and reduce the expression of inducible nitric oxide synthases. Polygalasaponin F can significantly i

HJC0197 selectively blocks cAMP-induced Epac activation. HJC0197 is an effective exchange protein. Which straightly activated by cAMP (Epac) antagonist (IC50=5.9 μM for Epac2).

Abaloparatide (BA 058), a parathyroid hormone receptor 1 (PTHR1) analog and selective activator, promotes Gs/cAMP signaling and β-arrestin recruitment, thereby enhancing bone formation and improving cortical structure in mice. This compound holds potential for osteoporosis research [1] [2].

Panaxydol has anti-cancer activity, can inhibit the growth and apoptosis of cancer cells, the signaling mechanisms involve a [Ca(2+)](i) increase, JNK and p38 MAPK activation, cAMP, MAP kinase and ROS generation through NADPH oxidase and mitochondria.

Luteolin 7-sulfate, derived from the marine plant Phyllospadix iwatensis Makino, suppresses TYR gene expression by intervening in a signaling pathway involving the cAMP-responsive element binding protein (CREB) and microphthalmia-associated transcription factor (MITF). This inhibition ultimately leads to a decrease in melanin synthesis.

AH 23848 is a Thromboxane antagonist which accelerates inducible nitric oxide synthase degradation through attenuation of cAMP signaling in glomerular mesangial cells.

CG500354 plays a tumor suppressive role through the cAMP/CREB signaling pathway and is a novel inducer of neural differentiation and growth arrest in primary HUMAN GBM derived cells.

2-AHA-cAMP is an analog of the natural signaling molecule cAMP and an activator of cAMP-dependent protein kinase. It features a free terminal primary amine group that can be used for coupling to gels or fluorescent dyes.

Skyrin is a fungal metabolite characterized by a bisanthraquinone structure. It interferes with glucagon signaling through adenylate cyclase without binding to the glucagon receptor. At 10 μM, skyrin reduces both glucagon-stimulated cAMP production and glycogenolysis. It does not interfere with epinephrine or glucagon-like peptide 1 effects on these parameters.[1] Reference：[1]. Parker, J.C., McPherson, R.K., Andrews, K.M., et al. Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes. Diabetes 49, 2079-2086 (2012).

FFA2 allosteric agonist. Inhibits forskolin-induced cAMP increase and stimulates 35SGTPγS binding in biochemical assays (pEC50 values are 6.9 and 7.23, respectively). Binds at allosteric binding site. In functional assays, displays positive allosteric modulation of FFA-induced Gi signaling and negative allosteric modulation of FFA-induced Gq/G11 signaling. Inhibits lipolytic effect of isoproterenol (pEC50 = 5.03) and induces migration of human neutrophils in vitro. Bolognini et al (2016) A novel allosteric activator of free fatty acid 2 receptor displays unique Gi-functional bias. J.Biol.Chem. 291 18915 PMID:27385588 |Sergeev et al (2017) A single extracellular amino acid in free fatty acid receptor 2 defines antagonist species selectivity and G protein selection bias. Sci.Rep. 7 13741 PMID:29061999

OX04528 is an orally active and potent GPR84 biased agonist.OX04528 inhibits cAMP signaling and may be useful in cancer research.

15(R)-Prostaglandin D2 functions as a DP(2) receptor (Prostaglandin Receptor) agonist with potential roles in prostatic hormone signaling and exhibits anti-inflammatory properties. It enhances actin polymerization in human eosinophils and elevates cAMP levels in platelets [1].

Serpinin, an agonist of the protease inhibitor Nexin-1 (PN-1), upregulates PN-1 expression via the cAMP-PKA-Sp1 signaling pathway, facilitating granule biogenesis in endocrine cells. It is employed in research on secretory function regulation [1]. Serpinin selectively targets β-adrenergic receptors, particularly interacting with β1-adrenergic receptors to activate the AC-cAMP-PKA pathway, thereby regulating myocardial systolic and diastolic function. Additionally, pGlu-serpinin upregulates Bcl2 mRNA transcription and provides neuroprotective effects [2].

AZ7976 (Compound 42), a potent and highly selective agonist for Relaxin Family Peptide Receptor 1 (RXFP1) with a pEC 50 value greater than 10.5, operates through an allosteric mechanism to enhance RXFP1's cAMP signaling, which physiologically elevates heart rate. This property makes AZ7976 a valuable tool in cardiovascular disease research [1].

2'-O-Me-cAMP is an analog of the natural signaling molecule cAMP and serves as a selective activator for the cAMP-activated exchange factor (Epac), characterized by its low membrane permeability.

8-Br-2'-O-Me-cAMP is an analog of the signaling molecule cAMP. It acts as an agonist for cAMP-activated exchange factors (Epac), yet unlike cAMP, it does not activate PKA.

8-CPT-cAMP-AM is a highly membrane-permeable analog of the signaling molecule cAMP. It serves as an activator for both cAMP and cGMP-dependent protein kinases, as well as Epac (exchange protein activated by cAMP).

8-pMeOPT-2'-O-Me-cAMP is an analog of the signaling molecule cAMP and serves as an effective stimulator of the cAMP-activated exchange factors (Epac). Unlike cAMP, it does not activate PKA.

WAY-181187 (SAX-187) oxalate is a selective and potent agonist of the 5-HT6 receptor (Ki: 2.2 nM; EC50: 6.6 nM) that mediates 5-HT6 receptor-dependent signaling pathways, including cAMP, Fyn, and ERK1 2 kinases.

VIP(6-28)(human, rat, porcine, bovine) is a potent antagonist that counteracts the effects of exogenous vasoactive intestinal peptide (VIP) on cyclic adenosine monophosphate (cAMP) signaling.

L-858,051 is a water-soluble analog of forskolin , a cell-permeant activator of adenylate cyclase. L-858,051 activates adenylate cyclase (EC50 = 3 μM), inhibits glucose transport, and blocks cytochalasin B binding in rat adipocyte membranes. L-858,051 is used to activate adenylate cyclase and initiate signaling through elevated cAMP synthesis in a variety of cell types in culture.

GLP-1R modulator L7-028 is a variant that enhances affinity for GLP-1 and (cAMP) signaling.

Compound 4h, also known as 5-HT7R antagonist 2, is a selective inhibitor of the 5-HT7R that disrupts both G protein and β-arrestin signaling pathways. It exhibits a K_i value of 67 nM, with IC_50 values of 2.59 μM in cAMP assays and 39.57 μM in Tango tests. This antagonist is noted for its potential to mitigate repetitive behaviors associated with autism spectrum disorder (ASD) and to foster the restoration of neurogenesis impaired by ASD [1]. Pharmacokinetic analysis in ICR male mice following intravenous and intraperitoneal administration shows a T_max of 0.08 hours and 0.25 hours, a T_1 2 of 0.77 hours and 1.06 hours, and a C_max of 33.07 ng mL and 156.44 ng mL, respectively. The AUC_last was recorded at 28.31 ng·h mL and 143.27 ng·h mL, with a clearance rate (CL) of 41.61 L h kg for intravenous administration. The volume of distribution at steady state (V_ss) was 32.43 L kg, the mean residence time (MRT) was 0.79 hours and 0.93 hours, and the bioavailability (F) was calculated at 50.60% [1].

Negative control for st-Ht31 . Gorshkov et al (2017) AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons. Nat.Chem.Biol. 13 425 PMID:28192412 |Vijayaraghavan et al (1997) Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. J.Biol.Chem. 272 4747 PMID:9030527 |Vincent et al (2017) Signaling: Spatial regulation of axonal cAMP. Nat.Chem.Biol. 13 348 PMID:28328917

Gliotoxin, a Wnt signaling pathway inhibitor, induces growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway.

Trans-caffeic acid stearyl ester is posited to inhibit melanogenesis signaling while suppressing cAMP levels and, subsequently, MC1R, MITF, tyrosinase, TRP-2 and TRP-1 down-regulation, resulting in the suppression of tyrosinase activity, DOPA oxidase activity and melanin synthesis.

BMS-470539 dihydrochloride is a selective and highly potent melanocortin 1 receptor (MC-1 R) agonist with anti-inflammatory activity. BMS-470539 attenuates oxidative stress and neuronal apoptosis via the MC1R cAMP PKA Nurr1 signaling pathway in a neonatal hypoxia-ischemia rat model.

Hcyb1 is a potent and specific inhibitor of phosphodiesterase 2 (PDE2). It exhibits a high degree of selectivity for inhibiting PDE2A with an IC50 value of 0.57 μM. In addition, Hcyb1 displays over 250-fold selectivity against other recombinant members of the PDE family. Moreover, its pharmacological actions include neuroprotective and antidepressant-like effects, which are believed to be mediated through the cAMP/cGMP-CREB-BDNF signaling pathway [1].

NY0116 is an agonist of the neuromedin U receptor 2 (NMUR2), exhibiting EC50 values of 27.76 μM for hNMUR1 and 13.61 μM for hNMUR2. In NMUR2 stably expressing HEK293 cells, NY0116 reduces cAMP levels while enhancing calcium signaling [1].

8-CPT-6-Phe-cAMP is a potent analog of the signaling molecule cAMP and a powerful activator of protein kinase A (PKA).

Wnt signaling is required for direct multiple biological processes and also plays key roles in the pathogenesis of various diseases. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Via generating a transcriptionally active complex with β-catenin, CREB acts as a mediator of Wnt signaling.ICG-001 is an inhibitor of β-catenin/CREB mediated transcription. The direct cellular target of ICG-001 is CREB. the inhibitory IC50of ICG-001 against β-catenin/CREB mediated transcription was 3 μM. ICG-001 treatment at the concentration of 25 μM for 24h significantly increased caspase activity in both colon cancer cell lines SW480 and HCT116 cell lines but not in normal colonic epithelial cells CCD-841Co. In a cell growth inhibition assay, the IC50s of ICG-001 against SW480 and HCT116 cells were 4.43 μM and 5.95 μM, respectively.In a SW620 nude mouse xenograft model, an water-soluble analog of ICG-001 given at the dose of 150 mg/kg i.v. once in every 2 days dramatically suppressed tumor growth. In a bleomycin-induced pulmonary fibrosis mice model, ICG-001 given at the dose of 5 mg/kg per day reversed pulmonary fibrosis. In a rat myocardial infarction model, ICG-001 was administrated subcutaneously at the dose of 50 mg/kg/day for 10 days which significantly improved cardiac contractile function after myocardial infarction in the rats.

6-Bnz-cAMP is a PKA-selective activator. It regulates the PKA dependent signaling pathways. The proliferative signaling pathway which activated by the 6-Bnz-cAMP involves activation of the epidermal growth factor receptor and ERK1/2. Extending the duratio

AP-C6 is a potent inhibitor of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase II (cGKII), with a pIC50 of 6.5. It inhibits human cGKII activity in vitro in a concentration-dependent manner and potentiates cAMP signaling through phosphodiesterase (PDE) inhibition [1].

SW106 is a selective antagonist of PTHR1-mediated cAMP signaling, not functioning as an inverse agonist on either PTHR1-T410P or PTHR1-H223R, which have activating mutations at the cytoplasmic ends of TMD helices-2 and -6, respectively.

8-Br-cAMP-AM, an analog of cyclic adenosine monophosphate (cAMP), activates two principal signaling pathways in the heart by mimicking the action of cAMP: protein kinase A (PKA) and the guanine nucleotide exchange factor (Epac) directly activated by cAMP. This compound is employed in the study of cardiac ischemia and reperfusion injury.