gmp-1

CP 461 (UNII-68OJX9I7DT) 是一种特异性 PDE2A 抑制剂，是一种新型促凋亡化合物，能抑制环 GMP 磷酸二酯酶，但不能抑制环氧化酶-1 或-2。CP 461 在体外可抑制多种人类肿瘤细胞系的生长，并选择性地诱导癌细胞系而不是正常细胞凋亡。

NS-2028 是一种高度选择性的可溶性鸟苷酸环化酶抑制剂。它抑制 3-吗啉代-sydnonimine 在人培养的脐静脉内皮细胞中形成环状 GMP，IC50为30mM。它抑制小鼠小脑匀浆和神经元 NO 合酶中的可溶性鸟苷酸环化酶活性，IC50分别为 17 和 20 mM。它可降低血管内皮生长因子诱导的血管生成和通透性。

CU-32 is an inhibitor of cyclic GMP-AMP (cGAMP) synthase (cGAS; IC50= 0.45 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. It is also selective for cGAS over toll-like receptors (TLRs) at 50 μM. CU-32 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)

Prepro-Atrial Natriuretic Factor (26-55) (human) 为促进肾皮质与髓质循环GMP水平上升的多肽，同时也增强肾腺苷酸环化酶的活性。

cGAMP (Cyclic GMP-AMPP) diammonium 是一种内源性第二信使，通过触发干扰素的产生来响应胞浆 DNA。它通过激活干扰素基因刺激因子（STING），启动信号级联，进而导致I型干扰素及其他免疫介质的生成。

Cyclic di-UMP is a pyrimidine-containing cyclic dinucleotide (CDN).1It is produced by bacterial cGAS DncV-like nucleotidyltransferases (CD-NTases), such as LpCdnE02 fromL. pneumophila, and binds to cGAS, in the apo or dsDNA-bound forms, with reduced affinity compared to 2'3'-cGAMP or 3'3'-cGAMP .1,2Cyclic di-UMP is intended for use as a negative control for cyclic di-GMP signaling. 1.Whiteley, A.T., Eaglesham, J.B., de Oliveira Mann, C.C., et al.Bacterial cGAS-like enzymes synthesize diverse nucleotide signalsNature564(7747)194-199(2019) 2.Hall, J., Ralph, E.C., Shanker, S., et al.The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibitionProtein Sci.26(12)2367-2380(2017)

IRAK4-IN-4 （化合物 15） 是白介素-1 受体相关激酶抑制剂，IC50为 2.8 nM。它还抑制环 GMP-AM 合酶 ，IC50为 2.1 nM。

Ribonuclease T1 (Rnase T1)，常用于生化研究。Ribonuclease T1 是一种内切酶，可特异性降解单链 RNA。Ribonuclease T1 能够形成核苷 2′，3′-环磷酸中间体，以切割 3′-鸟苷残基与邻近核苷 5′-OH 基团之间的磷酸二酯键，产生 3′-GMP 末端寡核苷酸。

cGAS-IN-4 (Compound 36) 是一种口服有效的环状 GMP-AMP 合酶 (cGAS) 抑制剂，对 h-cGAS 和 m-cGAS 的 IC50 分别为 32 nM 和 5.8 nM。在 THP-1 cell 细胞中，cGAS-IN-4 以 IC50 为 60 nM 抑制 cGAMP，从而提高细胞效能。在小鼠模型中，该化合物对 Concanavalin A 诱发的急性肝损伤展现抗炎作用。

5'-pApA is a linearized form of cyclic di-AMP, a bacterial second messenger that activates the host innate immune system through stimulator of interferon genes (STING).1,2,3,4It is a metabolite of cyclic di-AMP formedviahydrolysis by various phosphodiesterases (PDEs).55'-pApA is intended for use as a negative control for cyclic di-AMP signaling. 1.Burdette, D.L., Monroe, K.M., Sotelo-Troha, K., et al.STING is a direct innate immune sensor of cyclic-di-GMPNature478(7370)515-518(2011) 2.Parvatiyar, K., Zhang, Z., Teles, R.M., et al.DDX41 recognizes bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune responseNat. Immunol.13(12)1155-1161(2012) 3.Woodward, J.J., Iavarone, A.T., and Portnoy, D.A.c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon responseScience328(5986)1703-1705(2010) 4.Witte, C.E., Whiteley, A.T., Burke, T.P., et al.Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infectionmBio4(3)e00282-00213(2013) 5.Fahmi, T., Port, G.C., and Cho, K.H.c-di-AMP: An essential molecule in the signaling pathways that regulate the viability and virulence of gram-positive bacteriaGenes (Basel)8(8)197(2017)

Guanylin (human) TFA is a 15-amino acid peptide that serves as an endogenous activator of intestinal guanylate cyclase. This compound is primarily located in the gastrointestinal tract, where it regulates electrolyte and water transport in the intestinal and renal epithelia through a mechanism dependent on cyclic GMP. [1][2]

cGAS-IN-1（化合物C20）是一种黄酮类化合物，作为Cyclic GMP-AMP Synthase（cGAS）的抑制剂，其IC50分别为2.28 μM（针对人类cGAS）和1.44 μM（针对小鼠cGAS）。由于cGAS异常激活与众多免疫介导的炎症性疾病相关，cGAS-IN-1显示出了其抗炎潜力。

cGAS-IN-2 (compound 109) 作为一种高效的cGAS (Cyclic GMP-AMP Synthase) 抑制剂，展现出了对 h-cGAS 的强效抑制作用，具有 0.01512 μM 的IC50值。

Calmodulin antagonist-1 (W-7) is a calmodulin (CaM) antagonist that effectively inhibits calmodulin-activated Ca 2+ -phosphodiesterase (PDE) with an IC 50 of 28 μM. This compound also competitively inhibits trypsin-treated Ca 2+ -PDE with respect to cyclic GMP, exhibiting an IC 50 of 375 μM and a K i value of 300 μM.

eIF4E-IN-6（化合物4b）是一种针对eIF4E设计的抑制剂，可阻止其与cap mRNA的结合，其化学结构为GMP类似物。该化合物在Caco-2、HepG-2和MCF-7细胞系中显示出细胞毒性效果，其IC50值分别约为31、27和21 μM。

PF-04449613 is a phosphodiesterase 9A (PDE9A) inhibitor (IC50= 22 nM).1It is selective for PDE9A over PDE1C (IC50= >1,000 nM), as well as over a variety of other PDEs, inhibiting PDE2-8, -10, and -11 activity by less than 30% in a panel of enzymes, ion channels, and transporters at 1 μM but does inhibit the human dopamine transporter (DAT; Ki= 293 nM). PF-04449613 (0.1-100 mg kg, s.c.) increases cerebrospinal fluid (CSF) levels of cyclic GMP (cGMP) in rats. Subcutaneous administration of PF-04449613 (10 mg kg) increases the rate of dendritic spine formation and elimination in mouse primary motor cortex pyramidal neuronsin vivo.2It increases the average running speed of mice in an accelerating rotarod task, indicating improved motor learning, at the same dose. 1.Claffey, M.M., Helal, C.J., Verhoest, P.R., et al.Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitorsJ. Med. Chem.55(21)9055-9068(2012) 2.Lai, B., Li, M., Hu, A., et al.The phosphodiesterase 9 inhibitor PF-04449613 promotes dendritic spine formation and performance improvement after motor learningDev. Neurobiol.78(9)859-872(2018)

CU-76 is an inhibitor of cyclic GMP-AMP synthase (cGAS; IC50= 0.24 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. CU-76 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)

PF-9404C is the S-S diesteroisomer of a beta adrenergic receptors blocker with vasodilatory properties. PF9404C increased the formation of cyclic GMP from 3 pmol mg−1 protein in basal conditions, to 53 pmol mg−1 protein in 10 μM in rat aorta smooth muscle

8-CPT-Cyclic AMP (8-CPT-cAMP) sodium 是环 AMP 依赖性蛋白激酶的选择性激活剂。 8-CPT-Cyclic AMP sodium 也是有效的环 GMP 特异性磷酸二酯酶(PDE VA)抑制剂，IC50为 0.9 μM。 8-CPT-Cyclic AMP sodium 还抑制 PDE III 和 PDE IV，IC50分别为 24 和 25 μM。8-CPT-Cyclic AMP sodium 对 Epac 具有非常高的亲和力，是一种有效的Epac 活化剂。

GRP (14-27) (human, porcine, canine) 表现为铃蟾肽受体配体。其特异性结合受到 GTP 和 GDP 的抑制作用，但 GMP 对此无影响。

Cyclic di-GMP (c-di-GMP) diammonium 是一种STING 激活剂和无处不在的第二信使，调节生物膜的形成、运动和各种细菌的毒力。