cAMP accumulation

Ro 67-7476 是mGluR1的正变位调节剂，能增强表达 rat mGluR1a 的 HEK293 细胞中谷氨酸诱导的钙释放，EC50为 60.1 nM。它是 P-ERK1 2 激动剂，可以在外源添加谷氨酸的情况下激活 ERK1 2 磷酸化 (EC50=163.3 nM)。

Telcagepant（MK-0974，替卡吉泮）是一种口服的降钙素基因相关肽受体（CGRP, calcitonin gene-related peptide）拮抗剂，阻断CGRP受体并减少中枢神经系统的神经传递，用于研究偏头痛和减轻疼痛。

Siguazodan (SKF 94836) 是选择性的，口服有效的磷酸二酯酶 III 抑制剂，IC50为 117 nM。它可增加完整血小板中 cAMP 的积累，EC50为 18.88 μM。它也抑制苯肾上腺素诱导的 5-HT 释放，IC50为 4.2 μM。

3-Methylvaleric Acid 是一种食用级香料，存在于烟草中。3-Methylvaleric Acid 可增强 CHO-K1细胞和HEK293细胞中的细胞内cAMP 积累和CRE-荧光素酶活性。

Prostaglandin E1 (Alprostadil) 是一种前列腺素受体配体，对小鼠 EP1、EP2、EP3、EP4和 IP 的 Ki 值分别为 36、10、1.1、2.1 和 33 nM。它诱导血管舒张并抑制血小板聚集，可作为血管扩张剂用于外周血管疾病的研究。

Solabegron (GW 427353) 是一种β3肾上腺素能受体 (β3-AR)的选择性激动剂, 在中国仓鼠卵巢细胞中测得 EC50=22 nM，可用于研究膀胱过度活跃和肠易激综合征。

DD202-114 作为一种高效与选择性的 GLP1R 激动剂，可以促进 cAMP 的积累，降低血糖水平并减少食物摄入。它在 2 型糖尿病 (T2DM) 及肥胖症的研究中显示出潜在应用价值。

ECC5004是激活GLP-1R(GLP-1受体)的化学物质。此化合物在HEK293细胞系中（这些细胞表达了人类GLP-1R），能诱导cAMP的积累，其有效浓度中值（EC50）低于20 nM。

Trequinsin HCl是一种依赖于环磷酸腺苷(cAMP)的磷酸二酯酶(PDE) 3抑制剂。它促进cAMP的积累并增加细胞膜电容。

GLP-1R agonist 27 (compound 21) 是一种高效且具有口服活性的GLP-1R激动剂，能够促进环磷酸腺苷 (cAMP) 的积累，降低血糖水平和食物摄入量，具有研究肥胖和2型糖尿病 (T2DM) 的潜力。

FFA2 agonist-1 (Compound 4) 是一种游离脂肪酸受体 2 (FFA2 GPR43) 的激动剂，EC50为81 nM。在 β-arrestin-2 募集试验中，其EC50为1.2 μM，而在cAMP抑制试验中表现出的EC50为0.53 μM。该化合物能够激发食欲调节肽 YY (PYY) 粘膜反应，对脂肪积聚、肠道功能和食物摄入有抑制作用，适用于肥胖研究。

L-750,667 Trihydrochloride是一种选择性的 D4 多巴胺受体(D4 dopamine receptor)拮抗剂，具有高效的优点（Ki＝0.51 nM）。通过逆转多巴胺诱导的对cAMP（环磷酸腺苷，cyclic adenosine monophosphate）积累的抑制，L-750,667 Trihydrochloride 可对中枢神经系统中 D4 受体的进行研究。

Adenosine 5’-methylenediphosphate is an inhibitor of ecto-5’-nucleotidase, also known as CD73, with a Kivalue of 37 nM.1It inhibits cAMP accumulation induced by adenosine 5’-monophosphate , adenosine 5’-diphosphate , or adenosine 5’-triphosphate but not adenosine in VA-13 human fibroblasts when used at a concentration of 100 μM. Adenosine 5’-methylenediphosphate reduces proliferation of U138MG glioma cells, as well as inhibits the invasion and migration of MHCC97H hepatocellular carcinoma (HCC) cells in a migration assay.2,3It increases tumor infiltration of CD3+CD8+T cells and reduces tumor growth in a K1735 murine melanoma model when administered at a dose of 400 μg mouse.4 1.Bruns, R.F.Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosineNaunyn Schmiedebergs Arch. Pharmacol.315(1)5-13(1980) 2.Braganhol, E., Tamajusuku, A.S.K., Bernardi, A., et al.Ecto-5′-nucleotidase CD73 inhibition by quercetin in the human U138MG glioma cell lineBiochim. Biophys. Acta1770(9)1352-1359(2007) 3.Shali, S., Yu, J., Zhang, X., et al.Ecto 5′ nucleotidase (CD73) is a potential target of hepatocellular carcinomaJ. Cell Physiol.234(7)10248-10259(2018) 4.Forte, G., Sorrentino, R., Montinaro, A., et al.Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanomaJ. Immunol.189(5)2226-2233(2021)

Peptide YY (PYY) is a 36-amino acid peptide and anorectic gut hormone agonist for the neuropeptide Y receptors Y1, Y2, Y5, and Y6 with EC50 values of 0.7, 0.58, 1, and 0.8 nM, respectively, for supression of forskolin-induced cAMP accumulation. PYY is cleaved in vivo to PYY (3-36) . Release of PYY occurs postprandially in proportion to calorie intake from intestinal enteroendocrine L cells, indicating it may be a satiety signal. In humans, PYY inhibits food intake and gastrointestinal transit in both lean and obese subjects.

Pituitary adenylate cyclase-activating peptide (PACAP) (6-27) is a PACAP receptor antagonist with IC50 values of 1,500, 600, and 300 nM, respectively, for rat PAC1, rat VPAC1, and human VPAC2 recombinant receptors expressed in CHO cells. It binds to PACAP receptors on SH-SY5Y and SK-N-MC human neuroblastoma and T47D human breast cancer cells (IC50s = 24.5, 106, and 105 nM, respectively) and inhibits cAMP accumulation induced by PACAP (1-38) (Kis = 457, 102, and 283 nM, respectively, in SH-SY5Y, SK-N-MC, and T47D cells). In vivo, in newborn pigs, PACAP (6-27) (10 μM) inhibits vasodilation of pial arterioles induced by PACAP (1-27) and PACAP (1-38) . It also inhibits PACAP (1-27)-stimulated increases in plasma insulin and glucagon levels and pancreatic venous blood flow in dogs when administered locally to the pancreas at a dose of 500 μg.

Tyr-α-CGRP is an N-terminal extended tyrosinated analogue of α-calcitonin gene-related peptide . It binds to amylin receptors AMY1 and AMY3 in COS-7 cells expressing the human receptors (IC50s = 141 and 1.86 nM, respectively). Tyr-α-CGRP also binds to and stimulates cAMP accumulation in rat L6 myocytes (IC50 = 4 nM; EC50 = 12 nM). It also binds to rat brain and spleen membrane preparations (IC50s = 0.2 and 0.5 nM, respectively), induces positive chronotropic and inotropic effects in isolated right and left guinea pig atria (EC50s = 282 and 74 nM, respectively), and inhibits the twitch response in rat vas deferens (EC50 = 1.9 nM).

Selective medium-chain free fatty acid receptor GPR84 agonist (EC50 = 139 nM). Exhibits no response at GPR40, GPR41, GPR119 or GPR120 at 100 μM. Activates calcium mobilization, inhibits cAMP accumulation, and induces ERK1/2 phosphorylation, receptor desensitization and internalization in vitro. Liu et al (2016) Design and synthesis of 2-alkylpyrimidine-4,6-diol and 6-alkylpyridine-2,4-diol as potent GPR84 agonists. ACS Med.Chem.Lett. 7 579 PMID:27326330 |Zhang et al (2016) Discovery and characterization of a novel small-molecule agonist for medium-chain free fatty acid receptor G protein-coupled receptor 84. J.Pharmacol.Exp.Ther. 357 337 PMID:26962172

Bilaid C is a tetrapeptide μ-opioid receptor agonist (Ki= 210 nM in HEK293 cell membranes expressing the human receptor) that has been found inPenicillium.1It inhibits forskolin-induced cAMP accumulation by 77% in HEK293 cells expressing the human μ-opioid receptor when used at a concentration of 10 μM. Bilaid C induces inward rectifying potassium channel (Kir) currents in rat locus coeruleus slices that endogenously express high levels of the μ-opioid receptor (EC50= 4.2 μM). 1.Dekan, Z., Sianati, S., Yousuf, A., et al.A tetrapeptide class of biased analgesics from an Australian fungus targets the μ-opioid receptorProc. Natl. Acad. Sci. USA116(44)22353-22358(2019)

CAY10680 is a dopamine-sparing, benzothiazinone compound that selectively inhibits both MAO-B activity (IC50 = 34.9 nM in human) and adenosine A2A receptors (Ki = 39.5 nM in human). It demonstrates significantly less potent inhibitory values for other adenosine receptor subtypes (Kis > 1 μM) and MAO-A (IC50 ≥ 10 μM). At 1-20 μM, CAY10680 has been shown to abolish cAMP accumulation in CHO cells transfected with adenosine A2A receptors. In the central nervous system adenosine A2A receptor expression is localized to dopamine-innervated areas where heteromeric complexes are formed with dopamine D2 receptors. Because inhibition of adenosine A2A receptors has been shown to enhance D2 receptor function, the blockade of adenosine A2A receptors has emerged as a potential treatment for Parkinson's disease. An additional strategy in the treatment of Parkinson's disease has been to block the activity of monoamine oxidase B (MAO-B), the enzyme involved in dopamine catabolism.

Calcitonin is a peptide hormone that lowers blood calcium level and inhibits bone resorption. It belongs to the calcitonin family of peptides, which also includes amylin , calcitonin gene-related peptide , and adrenomedullin. The binding of salmon calcitonin to the human calcitonin receptor (CTR) is not modulated by receptor activity-modifying proteins (RAMPs), which influence affinity of human calcitonin to CTR. Salmon calcitonin binds to human CTR2 with IC50 values of 0.933, 0.224, 0.134, and 0.317 nM alone and with RAMP1, 2, or 3, respectively. It induces cAMP accumulation in COS-7 cells transfected with CTR2 (EC50 = 0.166 nM). Salmon calcitonin inhibits bone resorption by osteoclasts in a pit formation assay using rat bone slices (ID50 = 0.003 pg mL) and lowers calcium level in vivo in a bioassay of hypocalcemia in rats (ED15 = 33.9 mg kg). Formulations containing salmon calcitonin have been used to treat hypercalcemia, bone destruction by osteoporosis, and Paget's disease.

Galanin (Human) (Acetate)是一种含有30个氨基酸的神经肽和丙氨酸(GAL)受体激动剂。在表达重组人gal1受体的HEK293E 细胞(EC50= 0.031 nM)中，它抑制佛司可林诱导的cAMP 产生，并刺激表达重组人gal2受体的CHO 细胞(EC50= 12.3 nM)中肌醇磷酸的积累。Galanin (Human) (Acetate)诱导离体大鼠纵向眼底收缩，ec50值为13.8 nM。在大鼠福尔马林试验的第二阶段，鞘内给药人甘丙肽(3、10和30 nmol/只)可减少大鼠舔爪和退缩。

PSB-17365 is a potent GPR84 agonist. PSB-17365 exhibits EC50 values vs. GPR84 of 2.5nM in a cAMP accumulation assay, and 100nM in a β-arrestin 2 recruitment assay. No direct binding affinities are provided. PSB-17365 is selective for GPR84 compared to other free fatty acid receptors (FFAR1 and FFAR4). GPR84, a Gi protein-coupled receptor that is activated by medium-chain (hydroxy)fatty acids, appears to play an important role in inflammation, immunity, and cancer.

Tasimelteon-d5 is intended for use as an internal standard for the quantification of tasimelteon by GC- or LC-MS. Tasimelteon is a melatonin (MT) receptor agonist. It selectively binds MT1 and MT2 receptors over a panel of 160 additional receptors and enzymes at 10 µM. Tasimelteon inhibits forskolin-induced cAMP accumulation with EC50 values of 0.79 and 1 nM in NIH3T3 cells expressing the MT1 or MT2 receptor, respectively. Formulations containing tasimelteon have been used in the treatment of non-24-hour sleep-wake disorder.

K41498 TFA 是一种强选择性的CRF2 receptor 拮抗剂，其对人 CRF2α、CRF2β和 CRF1受体的Ki 值分别为 0.66 nM、0.62 nM 和425 nM。K41498 TFA 是 antisauvagine-30 (aSvg-30) 的类似物，可抑制 sauvagine 刺激的 cAMP 在 hCRF2α hCRF2β表达细胞中的积累。K41498 可用于低血压研究。