Page last updated: 2024-11-12

mre 269

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid: active form of NS-304 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ACT-333679 : A member of the class of pyrazines that is {4-[(propan-2-yl)(pyrazin-2-yl)amino]butoxy}acetic acid carrying two additional phenyl substituents at positions 5 and 6 on the pyrazine ring. The active metabolite of selexipag, an orphan drug used for the treatment of pulmonary arterial hypertension. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID Source	ID
PubMed CID	9931891
CHEMBL ID	239226
CHEBI ID	90848
SCHEMBL ID	676234
MeSH ID	M0525440

Synonyms (43)

Synonym
CHEMBL239226 ,
2-{4-[n-(5,6-diphenylpyrazin-2-yl)-n-isopropylamino]butyloxy}acetic acid
S5819
475085-57-5
gtpl5852
act-333679
act 333679
2-[4-[[5,6-di(phenyl)pyrazin-2-yl]-propan-2-ylamino]butoxy]acetic acid
mre 269
mre-269
SCHEMBL676234
BRD-K57391913-001-01-4
CHEBI:90848
{4-[(5,6-diphenylpyrazin-2-yl)(propan-2-yl)amino]butoxy}acetic acid
act333679
mre269
OJQMKCBWYCWFPU-UHFFFAOYSA-N ,
e9pc7n0did ,
unii-e9pc7n0did
(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid
J2.120.976G ,
HY-79593
CS-6104
AKOS027307832
2-{4-[(5,6-diphenylpyrazin-2-yl)(propan-2-yl)amino]butoxy}acetic acid
AS-72199
(4-((5,6-diphenylpyrazinyl)(1-methylethyl)amino)butoxy)acetic acid
acetic acid, (4-((5,6-diphenylpyrazinyl)(1-methylethyl)amino)butoxy)-
2-(4-(isopropyl(5,6-diphenylpyrazine-2-yl)amino)butoxy)acetic acid
{4-[(5,6-diphenyl-2-pyrazinyl)(isopropyl)amino]butoxy}acetic acid
BCP16833
2-(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid
Q27087731
bdbm50235387
EN300-384328
SB19699
2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]acetic acid
[4-[(5,6-diphenylpyrazinyl)(1-methylethyl)amino]butoxy]-acetic acid
HMS3748O13
A857157
mre-269(act-333679)
DTXSID801153092
2-[4-[(5,6-diphenyl-2-pyrazinyl)(1-methylethyl)amino]butoxy]acetic acid

Research Excerpts

Toxicity

Excerpt	Reference	Relevance
" The adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, nausea, jaw pain, and diarrhea."	( Clinical pharmacology, efficacy, and safety of selexipag for the treatment of pulmonary arterial hypertension. Bruderer, S; Dingemanse, J; Hurst, N; Remenova, T, 2017)	0.46

Pharmacokinetics

Excerpt	Reference	Relevance
" Possible pharmacodynamic and pharmacokinetic interactions between selexipag and warfarin in healthy individuals were investigated."	( Investigation of Potential Pharmacodynamic and Pharmacokinetic Interactions Between Selexipag and Warfarin in Healthy Male Subjects. Bruderer, S; Dingemanse, J; Mant, T; Mukai, H; Okubo, K, 2016)	0.43
"Steady-state levels of selexipag and ACT-333679 after repeated doses of 400 μg selexipag had no influence on the warfarin pharmacodynamic variables."	( Investigation of Potential Pharmacodynamic and Pharmacokinetic Interactions Between Selexipag and Warfarin in Healthy Male Subjects. Bruderer, S; Dingemanse, J; Mant, T; Mukai, H; Okubo, K, 2016)	0.43
" The present study evaluated the possible pharmacokinetic interactions of selexipag with gemfibrozil, a strong CYP2C8 inhibitor, and rifampicin, an inducer of CYP2C8."	( Effect of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects. Boehler, M; Bruderer, S; Dingemanse, J; Halabi, A; Petersen-Sylla, M; Remeňová, T, 2017)	0.46

Compound-Compound Interactions

Excerpt	Reference	Relevance
" However, due to its low dose and relatively low unbound exposure, selexipag has a low potential for causing drug-drug interactions."	( The metabolism and drug-drug interaction potential of the selective prostacyclin receptor agonist selexipag. Äänismaa, P; de Kanter, R; Delahaye, S; Gnerre, C; Ichikawa, T; Pfeifer, T; Seeland, S; Segrestaa, J; Treiber, A; Yamada, T, 2018)	0.48

Bioavailability

Excerpt	Reference	Relevance
"The aim of this single-center, open-label study was to assess the absolute bioavailability of an oral (tablet) versus intravenous (i."	( Absolute oral bioavailability of selexipag, a novel oral prostacyclin IP receptor agonist. Astruc, B; Dingemanse, J; Hurst, N; Kaufmann, P, 2017)	0.46
" The absolute oral bioavailability of selexipag (90% CI) was 49."	( Absolute oral bioavailability of selexipag, a novel oral prostacyclin IP receptor agonist. Astruc, B; Dingemanse, J; Hurst, N; Kaufmann, P, 2017)	0.46
" The bioavailability of selexipag after oral administration is approximately 50%."	( Absolute oral bioavailability of selexipag, a novel oral prostacyclin IP receptor agonist. Astruc, B; Dingemanse, J; Hurst, N; Kaufmann, P, 2017)	0.46

Dosage Studied

Excerpt	Relevance	Reference
"9 h, thus permitting oral dosing twice daily."	( Selexipag for the treatment of pulmonary arterial hypertension. Lang, IM; Skoro-Sajer, N, 2014)	0.4
" Pharmacokinetic properties of ACT-333679 permit twice-daily dosing of selexipag, providing a more convenient treatment compared to prostacyclin or its analogs."	( Clinical pharmacology, efficacy, and safety of selexipag for the treatment of pulmonary arterial hypertension. Bruderer, S; Dingemanse, J; Hurst, N; Remenova, T, 2017)	0.46
" The dosing flexibility afforded by oral selexipag may facilitate achieving the maximum therapeutic effect with acceptable tolerability in patients with PAH."	( Selexipag, a selective prostacyclin receptor agonist in pulmonary arterial hypertension: a pharmacology review. Honorato Pérez, J, 2017)	0.46

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

Role	Description
orphan drug	Any drug that has been developed specifically for treatment of a rare medical condition, the condition itself being known as an orphan disease.
platelet aggregation inhibitor	A drug or agent which antagonizes or impairs any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
prostacyclin receptor agonist	An agonist that binds to and activates prostacyclin receptors
vasodilator agent	A drug used to cause dilation of the blood vessels.
drug metabolite	null
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (6)

Class	Description
aromatic amine	An amino compound in which the amino group is linked directly to an aromatic system.
ether	An organooxygen compound with formula ROR, where R is not hydrogen.
pyrazines
sulfonamide	An amide of a sulfonic acid RS(=O)2NR'2.
tertiary amino compound	A compound formally derived from ammonia by replacing three hydrogen atoms by organyl groups.
monocarboxylic acid	An oxoacid containing a single carboxy group.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Inhibition Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Prostacyclin receptor	Homo sapiens (human)	IC50 (µMol)	0.2880	0.0084	0.0704	0.2880	AID1437828
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Prostacyclin receptor	Homo sapiens (human)	EC50 (µMol)	0.0220	0.0004	0.0545	0.3470	AID1437825
Prostaglandin D2 receptor	Homo sapiens (human)	EC50 (µMol)	0.1540	0.0006	0.4921	2.0590	AID1437826
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (14)

Process	via Protein(s)	Taxonomy
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	Prostacyclin receptor	Homo sapiens (human)
adenylate cyclase-activating G protein-coupled receptor signaling pathway	Prostacyclin receptor	Homo sapiens (human)
cell-cell signaling	Prostacyclin receptor	Homo sapiens (human)
negative regulation of platelet-derived growth factor receptor signaling pathway	Prostacyclin receptor	Homo sapiens (human)
response to lipopolysaccharide	Prostacyclin receptor	Homo sapiens (human)
negative regulation of smooth muscle cell proliferation	Prostacyclin receptor	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Prostacyclin receptor	Homo sapiens (human)
inflammatory response	Prostacyclin receptor	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Prostaglandin D2 receptor	Homo sapiens (human)
male sex determination	Prostaglandin D2 receptor	Homo sapiens (human)
sleep	Prostaglandin D2 receptor	Homo sapiens (human)
mast cell degranulation	Prostaglandin D2 receptor	Homo sapiens (human)
adenosine metabolic process	Prostaglandin D2 receptor	Homo sapiens (human)
cellular response to prostaglandin D stimulus	Prostaglandin D2 receptor	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Prostaglandin D2 receptor	Homo sapiens (human)
inflammatory response	Prostaglandin D2 receptor	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Process	via Protein(s)	Taxonomy
guanyl-nucleotide exchange factor activity	Prostacyclin receptor	Homo sapiens (human)
prostacyclin receptor activity	Prostacyclin receptor	Homo sapiens (human)
prostaglandin J receptor activity	Prostaglandin D2 receptor	Homo sapiens (human)
prostaglandin D receptor activity	Prostaglandin D2 receptor	Homo sapiens (human)
protein binding	Prostaglandin D2 receptor	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Process	via Protein(s)	Taxonomy
cytosol	Prostacyclin receptor	Homo sapiens (human)
plasma membrane	Prostacyclin receptor	Homo sapiens (human)
plasma membrane	Prostacyclin receptor	Homo sapiens (human)
plasma membrane	Prostaglandin D2 receptor	Homo sapiens (human)
membrane	Prostaglandin D2 receptor	Homo sapiens (human)
plasma membrane	Prostaglandin D2 receptor	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (37)

Assay ID	Title	Year	Journal	Article
AID301246	Oral bioavailability in Beagle dog at 3 mg/kg	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301236	Cmax in Sprague-Dawley rat at 10 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID309983	AUC (0 to 24 hrs) in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24	Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist.
AID301240	Half life in Beagle dog at 3 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301241	Half life in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301237	Cmax in Beagle dog at 3 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301244	AUC in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1437830	Half life in rat microsomes	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID301238	Cmax in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301229	Half life in Sprague-Dawley rat at 3 mg/kg, iv	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1437825	Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID309982	Half life in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24	Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist.
AID301234	Tmax in Beagle dog at 3 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID309980	Tmax in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24	Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist.
AID301230	Half life in Beagle dog at 1 mg/kg, iv	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1437824	Intrinsic activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level at 10 uM after 1 hr incubation by HTRF method relative to iloprost	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID301242	AUC in Sprague-Dawley rat at 10 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301243	AUC in Beagle dog at 3 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301232	AUC in Beagle dog at 1 mg/kg, iv	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301245	Oral bioavailability in Sprague-Dawley rat at 10 mg/kg	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1437829	Half life in human microsomes	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID301235	Tmax in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID301233	Tmax in Sprague-Dawley rat at 10 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1437826	Agonist activity at recombinant human DP1 receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID1437828	Agonist activity at IP receptor in human primary platelets assessed as inhibition of ADP-induced platelet aggregation	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID301231	AUC in Sprague-Dawley rat at 3 mg/kg, iv	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID309981	Cmax in cynomolgus monkey at 1 mg/kg, po	2007	Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24	Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist.
AID1437827	Intrinsic activity at recombinant human DP1 receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method relative to prostaglandin D2	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID1437823	Agonist activity at recombinant rat IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID1437822	Intrinsic activity at recombinant rat IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level at 10 uM after 1 hr incubation by HTRF method relative to iloprost	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID301239	Half life in Sprague-Dawley rat at 10 mg/kg, po	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1437853	Agonist activity at IP receptor in PAH patient-derived primary pulmonary arterial smooth muscle cells assessed as induction of cAMP levels after 1 hr by HTRF method	2017	Journal of medicinal chemistry, 02-09, Volume: 60, Issue:3	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.
AID301228	Inhibition of ADP-induced platelet aggregation in human platelet rich plasma	2007	Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21	Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
AID1346308	Human EP2 receptor (Prostanoid receptors)	2007	The Journal of pharmacology and experimental therapeutics, Sep, Volume: 322, Issue:3	2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug.
AID1346331	Rat IP receptor (Prostanoid receptors)	2007	The Journal of pharmacology and experimental therapeutics, Sep, Volume: 322, Issue:3	2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug.
AID1346350	Human IP receptor (Prostanoid receptors)	2007	The Journal of pharmacology and experimental therapeutics, Sep, Volume: 322, Issue:3	2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug.
AID1346427	Human EP4 receptor (Prostanoid receptors)	2007	The Journal of pharmacology and experimental therapeutics, Sep, Volume: 322, Issue:3	2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (33)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	4 (12.12)	29.6817
2010's	27 (81.82)	24.3611
2020's	2 (6.06)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 20.95

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	20.95 (24.57)
Research Supply Index	3.78 (2.92)
Research Growth Index	5.44 (4.65)
Search Engine Demand Index	18.60 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (20.95)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	10 (30.30%)	5.53%
Reviews	3 (9.09%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	20 (60.61%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
gemfibrozil [no description available]	4.45	1	1	aromatic ether	antilipemic drug
1-methyl-3-isobutylxanthine 1-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.	2.13	1	0	3-isobutyl-1-methylxanthine
oxazoles Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.. 1,3-oxazole : A five-membered monocyclic heteroarene that is an analogue of cyclopentadiene with O in place of CH2 at position 1 and N in place of CH at position 3.. oxazole : An azole based on a five-membered heterocyclic aromatic skeleton containing one N and one O atom.	3	1	0	1,3-oxazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene
pyrazines Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.	12.52	29	10	diazine; pyrazines	Daphnia magna metabolite
phenyl acetate phenyl acetate: The ester formed between phenol and acetic acid. Don't confuse with phenylacetic acid derivatives listed under PHENYLACETATES.. phenyl acetate : An acetate ester obtained by the formal condensation of phenol with acetic acid.	12.52	29	10	benzenes; phenyl acetates
lopinavir [no description available]	3.5	1	1	amphetamines; dicarboxylic acid diamide	anticoronaviral agent; antiviral drug; HIV protease inhibitor
n-nitrosomorpholinoaminoacetonitrile [no description available]	3	1	0
bmy 45778 BMY 45778: structure given in first source; partial prostacyclin agonist	3	1	0	bisoxazole	partial prostacyclin agonist
bmy 42393 BMY 42393: partial prostacyclin agonist	2.03	1	0
benzofurans Benzofurans: Compounds that contain a BENZENE ring fused to a furan ring.	2.08	1	0
ritonavir Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.. ritonavir : An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.	3.5	1	1	1,3-thiazoles; carbamate ester; carboxamide; L-valine derivative; ureas	antiviral drug; environmental contaminant; HIV protease inhibitor; xenobiotic
arachidonic acid icosa-5,8,11,14-tetraenoic acid : Any icosatetraenoic acid with the double bonds at positions 5, 8, 11 and 14.. arachidonate : A long-chain fatty acid anion resulting from the removal of a proton from the carboxy group of arachidonic acid.	2.13	1	0	icosa-5,8,11,14-tetraenoic acid; long-chain fatty acid; omega-6 fatty acid	Daphnia galeata metabolite; EC 3.1.1.1 (carboxylesterase) inhibitor; human metabolite; mouse metabolite
nadp [no description available]	3.56	1	1
quercetin [no description available]	2.41	1	0	7-hydroxyflavonol; pentahydroxyflavone	antibacterial agent; antineoplastic agent; antioxidant; Aurora kinase inhibitor; chelator; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; geroprotector; phytoestrogen; plant metabolite; protein kinase inhibitor; radical scavenger
bilirubin [no description available]	4.45	1	1	biladienes; dicarboxylic acid	antioxidant; human metabolite; mouse metabolite
dinoprostone prostaglandin E2 : Prostaglandin F2alpha in which the hydroxy group at position 9 has been oxidised to the corresponding ketone. Prostaglandin E2 is the most common and most biologically potent of mammalian prostaglandins.	2.13	1	0	prostaglandins E	human metabolite; mouse metabolite; oxytocic
dinoprost Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.. prostaglandin F2alpha : A prostaglandins Falpha that is prosta-5,13-dien-1-oic acid substituted by hydroxy groups at positions 9, 11 and 15. It is a naturally occurring prostaglandin used to induce labor.	2.13	1	0	monocarboxylic acid; prostaglandins Falpha	human metabolite; mouse metabolite
alprostadil [no description available]	2.07	1	0	prostaglandins E	anticoagulant; human metabolite; platelet aggregation inhibitor; vasodilator agent
6-ketoprostaglandin f1 alpha 6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.. 6-oxoprostaglandin F1alpha : A prostaglandin Falpha that is prostaglandin F1alpha bearing a keto substituent at the 6-position.	2.13	1	0	prostaglandins Falpha	human metabolite; mouse metabolite
prostaglandin e3 prostaglandin E3: Structure	2.07	1	0	prostaglandins E	human metabolite
iloprost Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of EPOPROSTENOL, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation.. iloprost : A carbobicyclic compound that is prostaglandin I2 in which the endocyclic oxygen is replaced by a methylene group and in which the (1E,3S)-3-hydroxyoct-1-en-1-yl side chain is replaced by a (3R)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl group. A synthetic analogue of prostacyclin, it is used as the trometamol salt (generally by intravenous infusion) for the treatment of peripheral vascular disease and pulmonary hypertension.	3.19	5	0	carbobicyclic compound; monocarboxylic acid; secondary alcohol	platelet aggregation inhibitor; vasodilator agent
beraprost beraprost: stable prostacyclin analog; structure given in first source. beraprost : An organic heterotricyclic compound that is (3aS,8bS)-2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan in which the hydrogens at positions 1R, 2R and 5 are replaced by (3S)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl, hydroxy and 3-carboxypropyl groups, respectively. It is a prostaglandin receptor agonist which is approved to treat pulmonary arterial hypertension in Asia.	2.08	1	0	enyne; monocarboxylic acid; organic heterotricyclic compound; secondary alcohol; secondary allylic alcohol	anti-inflammatory agent; antihypertensive agent; platelet aggregation inhibitor; prostaglandin receptor agonist; vasodilator agent
u 62840 U 62840: stereoisomeric benzindene prostaglandin analog; structure given in first source	3.01	4	0	carbotricyclic compound; carboxylic acid	antihypertensive agent; cardiovascular drug; human blood serum metabolite; platelet aggregation inhibitor; vasodilator agent; vitamin K antagonist
cfm 1571 CFM 1571: structure in first source	3	1	0	aromatic amide
selexipag selexipag: prostacyclin receptor agonist. selexipag : A member of the class of pyrazines that is N-(methanesulfonyl)-2-{4-[(propan-2-yl)(pyrazin-2-yl)amino]butoxy}acetamide carrying two additional phenyl substituents at positions 5 and 6 on the pyrazine ring. An orphan drug used for the treatment of pulmonary arterial hypertension. It is a prodrug for ACT-333679 (the free carboxylic acid).	12.31	28	10	aromatic amine; ether; monocarboxylic acid amide; N-sulfonylcarboxamide; pyrazines; tertiary amino compound	orphan drug; platelet aggregation inhibitor; prodrug; prostacyclin receptor agonist; vasodilator agent
ro3244794 RO3244794: structure in first source	2.08	1	0
beraprost sodium beraprost sodium : The organic sodium salt of beraprost. It is used in the treatment of chronic arterial occlusive disease and primary pulmonary hypertension in Japan.	2.03	1	0	organic sodium salt	anti-inflammatory agent; antihypertensive agent; platelet aggregation inhibitor; prostaglandin receptor agonist; vasodilator agent
natriuretic peptide, brain Natriuretic Peptide, Brain: A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.	4.45	1	1	polypeptide
warfarin Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.. warfarin : A racemate comprising equal amounts of (R)- and (S)-warfarin. Extensively used as both an anticoagulant drug and as a pesticide against rats and mice.. 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one : A member of the class of coumarins that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenyl-3-oxo-1-butyl group.	3.51	1	1	benzenes; hydroxycoumarin; methyl ketone
nephrin nephrin: gene nephrin is mutated in congenital nephrotic syndrome; amino acid sequence in first source; GenBank F19541; RefSeq NM_019459 (mouse), NM_004646 (human), NM_022628 (rat)	2.13	1	0
rifampin Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)	4.45	1	1	cyclic ketal; hydrazone; N-iminopiperazine; N-methylpiperazine; rifamycins; semisynthetic derivative; zwitterion	angiogenesis inhibitor; antiamoebic agent; antineoplastic agent; antitubercular agent; DNA synthesis inhibitor; EC 2.7.7.6 (RNA polymerase) inhibitor; Escherichia coli metabolite; geroprotector; leprostatic drug; neuroprotective agent; pregnane X receptor agonist; protein synthesis inhibitor

Condition	Relationship Strength	Studies	Trials
Vascular Diseases Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.	2.03	1	0
Pulmonary Hypertension [description not available]	8.2	9	1
Hypertension, Pulmonary Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.	8.2	9	1
Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	2.15	1	0
Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position.	2.15	1	0
Cerebral Infarction, Middle Cerebral Artery [description not available]	2.15	1	0
Apoplexy [description not available]	2.15	1	0
Cerebral Ischemia [description not available]	2.15	1	0
Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.	2.15	1	0
Infarction, Middle Cerebral Artery NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction.	2.15	1	0
Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)	2.15	1	0
Sclerosis, Systemic [description not available]	2.17	1	0
Scleroderma, Systemic A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.	2.17	1	0
Cryptogenic Fibrosing Alveolitis [description not available]	2.21	1	0
Idiopathic Pulmonary Fibrosis A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.	2.21	1	0
Heritable Pulmonary Arterial Hypertension [description not available]	3.93	1	0
Familial Primary Pulmonary Hypertension Familial or idiopathic hypertension in the PULMONARY CIRCULATION which is not secondary to other disease.	3.93	1	0
Kidney Failure A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.	2.13	1	0
Alloxan Diabetes [description not available]	2.13	1	0
Diabetic Glomerulosclerosis [description not available]	2.13	1	0
Diabetic Nephropathies KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.	2.13	1	0
Renal Insufficiency Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.	2.13	1	0
Liver Dysfunction [description not available]	3.51	1	1
Kidney Diseases Pathological processes of the KIDNEY or its component tissues.	3.51	1	1
Liver Diseases Pathological processes of the LIVER.	3.51	1	1
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	2.07	1	0

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