Compounds > rotigaptide
Page last updated: 2024-11-12

rotigaptide

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

Description

rotigaptide: an antiarrhythmic peptide [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9938933
CHEMBL ID450656
MeSH IDM0454382

Synonyms (31)

Synonym
355151-12-1
D05767
rotigaptide (usan)
zp-123
rotigaptide
gap-486
zp-123 (zealand)
CHEMBL450656
gap (wyeth)
gfa1w6ko7n ,
unii-gfa1w6ko7n
gap 486
rotigaptide [usan:inn]
zp123
glycinamide, n-acetyl-d-tyrosyl-d-prolyl-(4s)-4-hydroxy-d-prolylglycyl-d-alanyl-
n-acetyl-d-tyrosyl-d-prolyl-(4s)-4-hydroxy-d-prolylglycyl-d-alanylglycinamide
zp 123
gap 484
rotigaptide [inn]
rotigaptide [usan]
gtpl9214
(2r,4s)-1-[(2r)-1-[(2r)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]-n-[2-[[(2r)-1-[(2-amino-2-oxoethyl)amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-4-hydroxypyrrolidine-2-carboxamide
dipeptide 9f [pmid 19175320]
DB13067
zp1-23
ac-d-tyr-d-pro-d-hyp-gly-d-ala-gly-nh2
Q7370547
MS-30756
HY-106225
CS-0025346
AKOS040742576

Research Excerpts

Overview

Rotigaptide is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. It increases intercellular conductance in cardiac muscle cells by the prevention of dephosphorylation.

ExcerptReferenceRelevance
"Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. "( Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
Alimardanov, A; Butera, JA; Di, L; Hennan, JK; Huselton, C; Kerns, E; Larsen, BD; Liu, K; McDonald, L; Morgan, GA; Petersen, JS; Rossman, EI; Swillo, RE; Unwalla, R; Wang, Q, 2009)		1.8
"Rotigaptide (RG, ZP123) is a peptide analog that increases intercellular conductance in cardiac muscle cells by the prevention of dephosphorylation and thereby uncoupling of Connexin-43 (Cx43), possibly via action on unidentified protein phosphatases."( The Connexin 43 Regulator Rotigaptide Reduces Cytokine-Induced Cell Death in Human Islets.
Christensen, DP; Ghiasi, SM; Hansen, JB; Mandrup-Poulsen, T; Tyrberg, B, 2020)		1.58
"Rotigaptide (ZP123) is a selective gap junction modifier that increases cardiac gap junctional intercellular communication."( Rotigaptide (ZP123) improves atrial conduction slowing in chronic volume overload-induced dilated atria.
Haugan, K; Hirose, M; Kubota, I; Miyamoto, T; Nakayama, J; Shimojo, H; Takeishi, Y, 2006)		2.5

Treatment

Rotigaptide treatment reduced infarct size to 90 +/- 10% (P = 0.41), 67 +/- 7% ( P =0.005), and 82 (+7%) relative to vehicle-treated myocardial infarction rats. Treatment with rotigaptides increased the time to ischemia-induced asystole and suppressed dephosphorylation of Ser297 and Ser368 at 30 min of ischemia.

ExcerptReferenceRelevance
"Rotigaptide treatment producing steady state plasma levels of 0.8 +/- 0.1, 5.5 +/- 0.5, and 86 +/- 8 nmol/L had no effect on mortality, but reduced infarct size to 90 +/- 10% (P = 0.41), 67 +/- 7% (P = 0.005), and 82 +/- 7% (P = 0.13), respectively relative to vehicle-treated myocardial infarction rats (100 +/- 12%)."( Treatment with the gap junction modifier rotigaptide (ZP123) reduces infarct size in rats with chronic myocardial infarction.
Haugan, K; Hennan, JK; Kjølbye, AL; Marcussen, N; Nielsen, MS; Petersen, JS, 2006)		1.32
"Rotigaptide treatment initiated after a period of 30 minutes of metabolic stress produced a rapid and significant increase in CV compared to vehicle-treated time controls."( Rotigaptide (ZP123) reverts established atrial conduction velocity slowing.
Haugan, K; Hennan, JK; Kjølbye, AL; Petersen, JS, )		2.3
"Rotigaptide treatment significantly increased atrial conduction velocity in chronic volume overload hearts, however, rotigaptide did not decrease susceptibility to the induction of atrial tachyarrhythmias."( Rotigaptide (ZP123) improves atrial conduction slowing in chronic volume overload-induced dilated atria.
Haugan, K; Hirose, M; Kubota, I; Miyamoto, T; Nakayama, J; Shimojo, H; Takeishi, Y, 2006)		2.5
"Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed dephosphorylation of Ser297 and Ser368 at 30 min of ischemia."( Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123).
Andersen, S; Axelsen, LN; Hennan, JK; Holstein-Rathlou, NH; Jensen, ON; Kjølbye, AL; Larsen, BD; Mohammed, S; Nielsen, MS; Stahlhut, M, 2006)		0.88
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (7)

Assay IDTitleYearJournalArticle
AID370469Prevention of metabolic stress-induced conduction velocity slowing in Sprague-Dawley rat atrium at 10 uM by microelectrode based assay2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
AID370464Reduction of simulated ischemia-induced calcein uptake in rat C6 cells2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
AID370466Antiarrhythmic effect in calcium chloride-induced CD1 mouse arrhythmia model assessed as gap-junction intracellular communication re-establishment-mediated prolongation of time to onset of cardiac conduction block at 10 pmol/kg, iv relative to control2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
AID370465Antiarrhythmic effect in calcium chloride-induced CD1 mouse arrhythmia model assessed as gap-junction intracellular communication re-establishment-mediated prolongation of time to onset of cardiac conduction block at 1 pmol/kg, iv relative to control2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
AID370467Antiarrhythmic effect in calcium chloride-induced CD1 mouse arrhythmia model assessed as gap-junction intracellular communication re-establishment-mediated prolongation of time to onset of cardiac conduction block at 100 pmol/kg, iv relative to control2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
AID370480Antiarrhythmic effect in calcium chloride-induced CD1 mouse arrhythmia model assessed as gap-junction intracellular communication re-establishment-mediated prolongation of time to onset of cardiac conduction block at 10 mg/kg, po relative to control2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
AID370468Antiarrhythmic effect in calcium chloride-induced CD1 mouse arrhythmia model assessed as gap-junction intracellular communication re-establishment-mediated prolongation of time to onset of cardiac conduction block at 1 nmol/kg, iv relative to control2009Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4
Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (43)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's28 (65.12)29.6817
2010's12 (27.91)24.3611
2020's3 (6.98)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 23.79

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.

MetricThis Compound (vs All)
Research Demand Index23.79 (24.57)
Research Supply Index3.91 (2.92)
Research Growth Index4.37 (4.65)
Search Engine Demand Index26.67 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (23.79)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (6.52%)5.53%
Reviews7 (15.22%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other36 (78.26%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
amiodarone
Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.. amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias.		3.13101-benzofurans;
aromatic ketone;
organoiodine compound;
tertiary amino compound		cardiovascular drug
carvedilol
[no description available]		3.1310carbazoles;
secondary alcohol;
secondary amino compound		alpha-adrenergic antagonist;
antihypertensive agent;
beta-adrenergic antagonist;
cardiovascular drug;
vasodilator agent
ddt
1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane: structure in first source		2.0210benzenoid aromatic compound;
chlorophenylethane;
monochlorobenzenes;
organochlorine insecticide		bridged diphenyl acaricide;
carcinogenic agent;
endocrine disruptor;
persistent organic pollutant
serine
Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. serine : An alpha-amino acid that is alanine substituted at position 3 by a hydroxy group.		2.0310L-alpha-amino acid;
proteinogenic amino acid;
serine family amino acid;
serine zwitterion;
serine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
adenosine
quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit		3.1310adenosines;
purines D-ribonucleoside		analgesic;
anti-arrhythmia drug;
fundamental metabolite;
human metabolite;
vasodilator agent
tedisamil
tedisamil : A member of the class of diazabicyclononanes that is (1s,5s)-3,7-diazaspiro[bicyclo[3.3.1]nonane-9,1'-cyclopentane] in which the hydrogens at positions 3 and 7 are replaced by cyclopropylmethyl groups. It is a potassium channel blocker and an antiarrhythmic agent currently currently in development for the treatment of atrial fibrillation.		3.1310
proline
Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.. proline : An alpha-amino acid that is pyrrolidine bearing a carboxy substituent at position 2.		2.0510amino acid zwitterion;
glutamine family amino acid;
L-alpha-amino acid;
proline;
proteinogenic amino acid		algal metabolite;
compatible osmolytes;
Escherichia coli metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
tecadenoson
tecadenoson: an A1 adenosine receptor agonist		3.1310
piboserod
Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.		3.1310
dronedarone
Dronedarone: A non-iodinated derivative of amiodarone that is used for the treatment of ARRHYTHMIA.. dronedarone : A member of the class of 1-benzofurans used for the treatment of cardiac arrhythmias.		3.13101-benzofurans;
aromatic ether;
aromatic ketone;
sulfonamide;
tertiary amino compound		anti-arrhythmia drug;
environmental contaminant;
xenobiotic
benzofurans
Benzofurans: Compounds that contain a BENZENE ring fused to a furan ring.		3.1310
carbenoxolone sodium
Carbenoxolone: An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.		2.7730triterpenoid
antiarrhythmic peptide
antiarrhythmic peptide: atrial peptide from bovine atria; hexapeptide composed of hydroxyproline(1), proline(1), glycine(3) & alanine(1); both N-terminal & carboxy-terminal residues are glycine		7.9440
celivarone
celivarone: antiarrhythmic agent; structure in first source		3.1310
azd 7009
AZD 7009: an anti-arrhythmia agent; no further info available 10/2006		3.1310
ConditionIndicatedRelationship StrengthStudiesTrials
Auricular Fibrillation
[description not available]		05.69100
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		04.07140
Atrial Fibrillation
Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.		05.69100
Arrhythmia
[description not available]		05.6190
Arrhythmias, Cardiac
Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.		17.6190
Disease Exacerbation
[description not available]		02.3110
Cardiac Remodeling, Ventricular
[description not available]		02.7830
Cardiovascular Stroke
[description not available]		05.6261
Myocardial Infarction
NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).		05.6261
Ventricular Fibrillation
A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.		08.4670
Injury, Ischemia-Reperfusion
[description not available]		04.4311
Reperfusion Injury
Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.		09.4311
Cardiac Failure
[description not available]		02.4420
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		02.4420
Auricular Flutter
[description not available]		02.0510
Pleuropericarditis
Inflammation of both the PERICARDIUM and the PLEURA.		02.0510
Complication, Postoperative
[description not available]		02.0510
Atrial Flutter
Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).		02.0510
Pericarditis
Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.		02.0510
Postoperative Complications
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.		02.0510
Atrioventricular Nodal Re-Entrant Tachycardia
[description not available]		04.260
Tachycardia, Ventricular
An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).		04.260
A-V Dissociation
[description not available]		02.0110
Heart Disease, Ischemic
[description not available]		04.3370
Myocardial Ischemia
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).		04.3370
Extrasystole, Ventricular
[description not available]		02.0310
Injury, Myocardial Reperfusion
[description not available]		02.0310
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.0310
Chronic Illness
[description not available]		02.0310
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		02.0310
Asystole
[description not available]		02.4420
Heart Arrest
Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.		02.4420
Diathesis
[description not available]		02.0310
Atrial Ectopic Tachycardia
[description not available]		02.0310