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negative regulation of cAMP-mediated signaling

Definition

Target type: biologicalprocess

Any process which stops, prevents, or reduces the frequency, rate or extent of cAMP-mediated signaling. [GOC:jl]

Negative regulation of cAMP-mediated signaling is a critical cellular process that ensures appropriate and controlled responses to various stimuli. cAMP (cyclic adenosine monophosphate) is a ubiquitous second messenger that plays a crucial role in diverse cellular functions, including gene expression, cell growth, and metabolism. The cAMP signaling pathway is initiated by the activation of G protein-coupled receptors (GPCRs) by extracellular ligands. Ligand binding to GPCRs triggers a cascade of events involving the activation of adenylyl cyclase, an enzyme responsible for catalyzing the conversion of ATP to cAMP. Increased cAMP levels activate protein kinase A (PKA), a serine/threonine kinase that phosphorylates various downstream targets, leading to a multitude of cellular responses. To maintain cellular homeostasis and prevent excessive cAMP signaling, cells employ a variety of mechanisms to negatively regulate this pathway. These regulatory mechanisms encompass multiple levels, including:

**1. Regulation of GPCR activity:** GPCR desensitization and downregulation are crucial mechanisms for attenuating cAMP signaling. Desensitization involves phosphorylation of the activated GPCR by G protein-coupled receptor kinases (GRKs), leading to the recruitment of arrestin proteins. Arrestins bind to phosphorylated GPCRs, preventing further activation of G proteins and promoting internalization of the receptor. Downregulation involves the removal of GPCRs from the cell surface via endocytosis, decreasing the number of available receptors for ligand binding.

**2. Regulation of adenylyl cyclase activity:** Adenylyl cyclase activity can be regulated by multiple factors. One key mechanism involves the inhibitory G protein (Gi), which is activated by specific GPCRs. Gi inhibits adenylyl cyclase, reducing cAMP production. Furthermore, intracellular calcium levels can also regulate adenylyl cyclase activity, with high calcium levels often leading to inhibition.

**3. Regulation of cAMP degradation:** cAMP levels are tightly controlled by the enzyme phosphodiesterase (PDE), which catalyzes the hydrolysis of cAMP to inactive AMP. PDE activity can be regulated by various factors, including phosphorylation, protein-protein interactions, and second messengers like calcium.

**4. Regulation of PKA activity:** PKA activity can be regulated by several mechanisms, including: a) the binding of cAMP to regulatory subunits of PKA, which releases the catalytic subunits and activates their kinase activity. b) phosphorylation of PKA by other kinases, which can modulate its activity. c) interaction of PKA with scaffolding proteins, which can target PKA to specific subcellular locations.

**5. Regulation of downstream targets:** The cellular effects of cAMP signaling are mediated by the phosphorylation of downstream targets by PKA. These downstream targets include transcription factors, ion channels, and enzymes. The phosphorylation of these targets can either activate or inhibit their function, depending on the specific target.

**6. Negative feedback loops:** Many components of the cAMP signaling pathway are involved in negative feedback loops that help to dampen the signal. For example, PKA can phosphorylate and inhibit adenylyl cyclase, reducing cAMP production. Similarly, some downstream targets of PKA can inhibit the activity of GPCRs or adenylyl cyclase.

**In summary**, negative regulation of cAMP-mediated signaling is a complex and multifaceted process that involves multiple levels of control. These regulatory mechanisms ensure that cAMP signaling is appropriately balanced, preventing excessive or inappropriate activation of the pathway and maintaining cellular homeostasis. '"

Proteins (7)

ProteinDefinitionTaxonomy
Mu-type opioid receptorA mu-type opioid receptor that is encoded in the genome of cow. [OMA:P79350, PRO:DNx]Bos taurus (cattle)
cGMP-dependent 3',5'-cyclic phosphodiesteraseA cGMP-dependent 3,5-cyclic phosphodiesterase that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00408]Homo sapiens (human)
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11AA dual 3,5-cyclic-AMP and -GMP phosphodiesterase 11A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9HCR9]Homo sapiens (human)
Lysophosphatidic acid receptor 1A lysophosphatidic acid receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q92633]Homo sapiens (human)
cGMP-inhibited 3',5'-cyclic phosphodiesterase AA cGMP-inhibited 3,5-cyclic phosphodiesterase 3A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14432]Homo sapiens (human)
Nociceptin receptorA nociceptin receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:P41146]Homo sapiens (human)
Apelin receptorAn apelin receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35414]Homo sapiens (human)

Compounds (104)

CompoundDefinitionClassesRoles
my 5445MY 5445: potential platelet aggregation inhibitorpyridazines;
ring assembly
theophyllinedimethylxanthineadenosine receptor antagonist;
anti-asthmatic drug;
anti-inflammatory agent;
bronchodilator agent;
drug metabolite;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
fungal metabolite;
human blood serum metabolite;
immunomodulator;
muscle relaxant;
vasodilator agent
cilostamidecilostamide: selective inhibitor of cyclic AMP phosphodiesterase & platelet aggregation; structurequinolines
cilostazollactam;
tetrazoles
anticoagulant;
bronchodilator agent;
EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor;
fibrin modulating drug;
neuroprotective agent;
platelet aggregation inhibitor;
vasodilator agent
dipyridamoledipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots.

Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)
piperidines;
pyrimidopyrimidine;
tertiary amino compound;
tetrol
adenosine phosphodiesterase inhibitor;
EC 3.5.4.4 (adenosine deaminase) inhibitor;
platelet aggregation inhibitor;
vasodilator agent
9-(2-hydroxy-3-nonyl)adenine9-(2-hydroxy-3-nonyl)adenine: specific inhibitor of adenosine deaminase
etazolateetazolate : A pyrazolopyridine that is 1H-pyrazolo[3,4-b]pyridine which is substituted at positions 1, 4, and 5 by ethyl, 2-isopropylidenehydrazino, and ethoxycarbonyl groups, respectively. A phosphodiesterase IV inhibitor with antidepressant and anxiolytic properties.

Etazolate: A potent phosphodiesterase inhibitor proposed as an antipsychotic agent.
ethyl ester;
hydrazone;
pyrazolopyridine
alpha-secretase activator;
antidepressant;
antipsychotic agent;
anxiolytic drug;
GABA agent;
neuroprotective agent;
phosphodiesterase IV inhibitor
fluspirileneFluspirilene: A long-acting injectable antipsychotic agent used for chronic schizophrenia.diarylmethane
ibudilastpyrazolopyridine
amrinoneamrinone : A 3,4'-bipyridine substituted at positions 5 and 6 by an amino group and a keto function respectively. A pyridine phosphodiesterase 3 inhibitor, it is a drug that may improve the prognosis in patients with congestive heart failure.

Amrinone: A positive inotropic cardiotonic (CARDIOTONIC AGENTS) with vasodilator properties, phosphodiesterase 3 inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.
bipyridinesEC 3.1.4.* (phosphoric diester hydrolase) inhibitor
1-methyl-3-isobutylxanthine1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES

3-isobutyl-1-methylxanthine : An oxopurine that is xanthine which is substituted at positions 1 and 3 by methyl and isobutyl groups, respectively.
3-isobutyl-1-methylxanthine
loperamideloperamide : A synthetic piperidine derivative, effective against diarrhoea resulting from gastroenteritis or inflammatory bowel disease.

Loperamide: One of the long-acting synthetic ANTIDIARRHEALS; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally.
monocarboxylic acid amide;
monochlorobenzenes;
piperidines;
tertiary alcohol
anticoronaviral agent;
antidiarrhoeal drug;
mu-opioid receptor agonist
losartanlosartan : A biphenylyltetrazole where a 1,1'-biphenyl group is attached at the 5-position and has an additional trisubstituted imidazol-1-ylmethyl group at the 4'-position

Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
biphenylyltetrazole;
imidazoles
angiotensin receptor antagonist;
anti-arrhythmia drug;
antihypertensive agent;
endothelin receptor antagonist
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first sourcechromones;
morpholines;
organochlorine compound
autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector
milrinonebipyridines;
nitrile;
pyridone
cardiotonic drug;
EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor;
platelet aggregation inhibitor;
vasodilator agent
papaverinepapaverine : A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.

Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
benzylisoquinoline alkaloid;
dimethoxybenzene;
isoquinolines
antispasmodic drug;
vasodilator agent
pentoxifyllineoxopurine
proxyphyllineoxopurine
pyrimethamineMaloprim: contains above 2 cpdsaminopyrimidine;
monochlorobenzenes
antimalarial;
antiprotozoal drug;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.methoxybenzenes
roliprampyrrolidin-2-onesantidepressant;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor
sulmazolesulmazole : An imidazopyridine that is 1H-imidazo[4,5-b]pyridine which is substituted at position 2 by a 2-methoxy-4-(methylsulfinyl)phenyl group. An A1 adenosine receptor antagonist, it was formerly used as a cardiotonic agent.

sulmazole: structure given in first source
imidazopyridine;
sulfoxide
adenosine A1 receptor antagonist;
cardiotonic drug;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor
trequinsintrequinsin: RN given refers to parent cpd; structure given in first sourcepyridopyrimidine
vesnarinoneorganic molecular entity
zardaverinezardaverine : A pyridazinone derivative in which pyridazin-3(2H)-one is substituted at C-6 with a 4-(difluoromethoxy)-3-methoxyphenyl group. It is a phosphodiesterase inhibitor, selective for PDE3 and 4.

zardaverine: structure given in first source
organofluorine compound;
pyridazinone
anti-asthmatic drug;
bronchodilator agent;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
peripheral nervous system drug
2-chloroadenosine5-chloroformycin A: structure given in first sourcepurine nucleoside
cycloguanilcycloguanil : A triazine in which a 1,6-dihydro-1,3,5-triazine ring is substituted at N-1 by a 4-chlorophenyl group, at C-2 and -4 by amino groups and at C-6 by gem-dimethyl groups. A dihydrofolate reductase inhibitor, it is a metabolite of the antimalarial drug proguanil.

cycloguanil: the active metabolite of proguanil; antifolate drug; structure in first source
triazinesantifolate;
antiinfective agent;
antimalarial;
antiparasitic agent;
antiprotozoal drug;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
9-benzyladenine
cladribineorganochlorine compound;
purine 2'-deoxyribonucleoside
antineoplastic agent;
immunosuppressive agent
eg 626phthalazinol: RN given refers to parent cpd; do not confuse with phthalazinol: 62054-23-3; thromboxane A2 antagonistphthalazines
enoximoneEnoximone: A selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with CONGESTIVE HEART FAILURE.aromatic ketone
atomoxetineatomoxetine : A secondary amino compound having methyl and 3-(2-methylphenoxy)-3-phenylpropan-1-yl substituents.aromatic ether;
secondary amino compound;
toluenes
adrenergic uptake inhibitor;
antidepressant;
environmental contaminant;
xenobiotic
piroximonepiroximone: structure in first source
2-(2-methoxy-4-(methylsulfinyl)phenyl)-1h-imidazo(4,5-c)pyridine2-(2-methoxy-4-(methylsulfinyl)phenyl)-1H-imidazo(4,5-c)pyridine: RN & structure given in first source; RN given refers to parent cpd; closely related to sulmazoleimidazoles
imazodanimazodan: RN & structure given in first source;
nitraquazonenitraquazone: structure given in first source
bufrolinbufrolin: inhibits the release of histamine; proposed for treatment of hay fever, asthma and skin allergies; minor descriptor (79-86); on line & INDEX MEDICUS search PHENANTHROLINES (79-86); RN given refers to parent cpd
u 69593U 69593: selective ligand for opioid K-receptor

U69593 : A monocarboxylic acid amide obtained by formal condensation between the carboxy group of phenylacetic acid and the secodary amino group of (5R,7S,8S)-N-methyl-7-(pyrrolidin-1-yl)-1-oxaspiro[4.5]decan-8-amine.
monocarboxylic acid amide;
N-alkylpyrrolidine;
organic heterobicyclic compound;
oxaspiro compound
anti-inflammatory agent;
diuretic;
kappa-opioid receptor agonist
tadalafilbenzodioxoles;
pyrazinopyridoindole
EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor;
vasodilator agent
clofarabineadenosines;
organofluorine compound
antimetabolite;
antineoplastic agent
dioctanoylphosphatidic aciddioctanoylphosphatidic acid: structure given in first source1,2-diacyl-sn-glycerol 3-phosphate;
octanoate ester
y 590
9-(2-hydroxy-3-nonyl)adenine(2R,3S)-EHNA : EHNA of absolute configuration 2R,3S. Selective inhibitor of cGMP-stimulated phosphodiesterase (PDE2) (IC50 = 0.8 - 4 mM). Also a potent inhibitor of adenosine deaminase.EHNAEC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
EC 3.5.4.4 (adenosine deaminase) inhibitor
9-(2-hydroxy-3-nonyl)adenine(2S,3R)-EHNA : EHNA of absolute configuration 2S,3R.EHNA
cilomilastmethoxybenzenes
rp 73401piclamilast : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 3-(cyclopentyloxy)-4-methoxybenzoic acid with the primary amino group of 3,5-dichloropyridin-4-amine.

piclamilast: an antiasthmatic agent and phosphodiesterase 4 inhibitor; structure in first source
aromatic ether;
benzamides;
chloropyridine;
monocarboxylic acid amide
anti-asthmatic drug;
anti-inflammatory agent;
bronchodilator agent;
phosphodiesterase IV inhibitor
8-methoxymethyl-3-isobutyl-1-methylxanthine8-methoxymethyl-3-isobutyl-1-methylxanthine: inhibitor of phosphodiesterase Ioxopurine
vinpocetinevinpocetine: whole issue of Arzneim Forsch (23 articles) discuss this drug; Arzneim Forsch 26(10a);1976; RN given refers to parent cpd with unspecified isomeric designationalkaloidgeroprotector
rolipram(-)-rolipram : The (R)-enantiomer of rolipram.rolipram
roflumilastaromatic ether;
benzamides;
chloropyridine;
cyclopropanes;
organofluorine compound
anti-asthmatic drug;
phosphodiesterase IV inhibitor
4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2h)-pyridazinone4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone: RN & structure given in first source
indolidanindolidan: structure given in first source
morphineMeconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.morphinane alkaloid;
organic heteropentacyclic compound;
tertiary amino compound
anaesthetic;
drug allergen;
environmental contaminant;
geroprotector;
mu-opioid receptor agonist;
opioid analgesic;
plant metabolite;
vasodilator agent;
xenobiotic
j 113397J 113397: an opioid receptor-like 1 (ORL1), orphanin FQ, and nociceptin receptor antagonist; structure in first source
lysophosphatidic acid1-oleoyl-sn-glycerol 3-phosphate : A 1-acyl-sn-glycerol 3-phosphate having oleoyl as the 1-O-acyl group.

lysophosphatidic acid : A member of the class of lysophosphatidic acids obtained by hydrolytic removal of one of the two acyl groups of any phosphatidic acid. A 'closed' class.

lysophosphatidic acid: RN given refers to parent cpd
1-acyl-sn-glycerol 3-phosphate
n-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamideN-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide: a nociceptin antagonist; structure in first sourceaminoquinoline
naltrexonenaltrexone : An organic heteropentacyclic compound that is naloxone substituted in which the allyl group attached to the nitrogen is replaced by a cyclopropylmethyl group. A mu-opioid receptor antagonist, it is used to treat alcohol dependence.

Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
cyclopropanes;
morphinane-like compound;
organic heteropentacyclic compound
antidote to opioid poisoning;
central nervous system depressant;
environmental contaminant;
mu-opioid receptor antagonist;
xenobiotic
bemoradanbemoradan: RN & structure given in first source
enkephalin, ala(2)-mephe(4)-gly(5)-peptide
norbinaltorphiminenorbinaltorphimine: kappa opiate receptor antagonist; structure given in first sourceisoquinolines
dermorphindermorphin: opiate-like peptide present in amphibian skinoligopeptide
1,3-dihydro-7,8-dimethyl-2h-imidazo(4,5-b)quinolin-2-one1,3-dihydro-7,8-dimethyl-2H-imidazo(4,5-b)quinolin-2-one: structure given in first source
lysophosphatidic acid
naltrindolenaltrindole: delta opioid receptor antagonistisoquinolines
N-(1,3-benzodioxol-5-ylmethyl)-6-chloro-4-quinazolinaminequinazolines
pmx 53
4-oxo-6-((pyrimidin-2-ylthio)methyl)-4h-pyran-3-yl 4-nitrobenzoate4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate: structure in first sourcenitrobenzoic acid
sch 351591SCH 351591: a phosphodiesterase 4 inhibitor; structure in first source

SCH-351591 : An aromatic amide resulting from the formal condensation of the carboxy group of 8-methoxy-2-(trifluoromethyl)quinoline-5-carboxylic acid with the primary amino group of 3,5-dichloropyridin-4-amine 1-oxide. It is a potent inhibitor of phosphodiesterase IV (PDE4).
camostat4-hydroxyatomoxetine: an atomoxetine metabolite; structure in first sourcearomatic ether;
phenols
ci 1044CI 1044: inhibits PDE4; structure in first source
ro 64-6198Ro 64-6198: an orphanin FQ/nociceptin receptor agonist; structure in first source
t 1032T 1032: a cyclic GMP phosphodiesterase-5 inhibitor; structure in first source
sr 14150SR 14150: mixed NOP and mu-opioid receptor ligand and antinociceptive; structure in first source
sb-612111
diacylglycerol pyrophosphate1,2-dioctanoyl-sn-glycerol 3-diphosphate : A 1,2-diacyl-sn-glycerol 3-diphosphate in which both of the phosphatidyl acyl groups are specified as octanoyl.1,2-diacyl-sn-glycerol 3-diphosphate;
octanoate ester
ki164253-[({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-1,2-oxazol-5-yl]phenyl}methyl)sulfanyl]propanoic acid : A member of the class of isoxazoles that is the carbamate ester obtained by formal condensation of the carboxy group of 1-(2-chlorophenyl)ethyl hydrogen carbonate with the amino group of 3-({[4-(4-amino-3-methyl-1,2-oxazol-5-yl)phenyl]methyl}sulfanyl)propanoic acid.carbamate ester;
isoxazoles;
monocarboxylic acid;
monochlorobenzenes;
organic sulfide
naluzotannaluzotan: an antidepressant and anti-anxiety agent; structure in first source
losartan potassiumErythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
cebranopadol
(2R,3S)-EHNA hydrochloride(2R,3S)-EHNA hydrochloride : A hydrochloride salt obtained by reaction of (2R,3S)-EHNA with one equivalent of hydrochloric acid. Selective inhibitor of cGMP-stimulated phosphodiesterase (PDE2) (IC50 = 0.8 - 4 mM). Also a potent inhibitor of adenosine deaminase.hydrochlorideEC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
EC 3.5.4.4 (adenosine deaminase) inhibitor
a 803467A 803467: an Nav1.8 sodium channel blocker; structure in first source
nociceptinorganic molecular entity;
polypeptide
human metabolite;
rat metabolite
pf 04217903quinolines
3-(2,5-dimethoxyphenyl)-6-(3,4-dimethoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazinetriazoles
1-(1-(1-methylcyclooctyl)-4-piperidinyl)-2-((3r)-3-piperidinyl)-1h-benzimidazole1-(1-(1-methylcyclooctyl)-4-piperidinyl)-2-((3R)-3-piperidinyl)-1H-benzimidazole: anxiolytic agent; structure in first source
apelin-13 peptideapelin-13 : A 13 amino acid oligopeptide which is the ligand for the apelin receptor (also known as the APJ receptor). It exhibits hypotensive and neuroprotective effects, and may be a potential prognostic biomarker for acute ischemic stroke and multiple sclerosis.

apelin-13 peptide: amino acid sequence in first source
oligopeptideantihypertensive agent;
autophagy inhibitor;
biomarker;
human metabolite;
neuroprotective agent
p-Glu-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phep-Glu-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe : A thirteen-membered polypeptide consisting of p-Glu, Arg, Pro, Arg, Leu, Ser, His, Lys, Gly, Pro, Met, Pro and Phe residues joined in sequence.polypeptideapoptosis inhibitor;
human metabolite;
neuroprotective agent
pf-044189481-(4-fluorobenzoyl)-3-(((6-methoxy-2-naphthyl)oxy)methyl)azetidine-3-carboxylic acid: structure in first source
vpc32183VPC32183: lysophosphatidic acid (LPA) receptor antagonist
nitd 609NITD 609: an antimalarial and coccidiostat; structure in first source
an2728crisaborole : A member of the class of benzoxaboroles that is 5-hydroxy-1,3-dihydro-2,1-benzoxaborole in which the phenolic hydrogen has been replaced by a 4-cyanophenyl group. A phosphodiesterase 4 inhibitor that is used for treatment of mild to moderate atopic dermatitis in children and adults.

crisaborole: NSAID, Dermatologic Agent; structure in first source
aromatic ether;
benzoxaborole;
nitrile
antipsoriatic;
non-steroidal anti-inflammatory drug;
phosphodiesterase IV inhibitor
cc-1151-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one: an mTOR kinase inhibitor; structure in first source
chf6001tanimilast: a phosphodiesterase-4 inhibitor; structure in first source
cyclic gmp3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine.

Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
3',5'-cyclic purine nucleotide;
guanyl ribonucleotide
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
sildenafilsildenafil : A pyrazolo[4,3-d]pyrimidin-7-one having a methyl substituent at the 1-position, a propyl substituent at the 3-position and a 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl group at the 5-position.piperazines;
pyrazolopyrimidine;
sulfonamide
EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor;
vasodilator agent
zaprinastzaprinast: anaphylaxis inhibitor; structuretriazolopyrimidines
vardenafilvardenafil : The sulfonamide resulting from formal condensation of the sulfo group of 4-ethoxy-3-(5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one-2-yl)benzenesulfonic acid and the secondary amino group of 4-ethylpiperazine.imidazotriazine;
N-alkylpiperazine;
N-sulfonylpiperazine
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
vasodilator agent
Imidazosagatriazinonepyrazolopyrimidine
bl 4162aanagrelide : A 1,5-dihydroimidazo[2,1-]quinazoline having an oxo substituent at the 2-position and chloro substituents at the 6- and 7-positions.

anagrelide: imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation; used for thrombocythemia; structure in first source
imidazoquinazolineanticoagulant;
antifibrinolytic drug;
cardiovascular drug;
platelet aggregation inhibitor
1,5-dihydro-7-(1-piperidinyl)-imidazo(2,1-b)quinazolin-2(3h)-one1,5-dihydro-7-(1-piperidinyl)-imidazo(2,1-b)quinazolin-2(3H)-one: a potent inhibitor of platelet aggregation
quazinone
lixazinonelixazinone: structure given in first source
6-((3s,4s)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-1-(tetrahydro-2h-pyran-4-yl)-1,5-dihydro-4h-pyrazolo(3,4-d)pyrimidin-4-one
bay 60-7550