Page last updated: 2024-11-12

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ilys-prolyl-alaninamide

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Description

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide: FE-200486 is the acetate salt [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID16136245
CHEMBL ID415606
CHEBI ID135961
SCHEMBL ID1397034
SCHEMBL ID21050504
MeSH IDM0394390

Synonyms (51)

Synonym
firmagon
CHEBI:135961
degarelix
CHEMBL415606 ,
fe200486 (as acetate salt)
DB06699
D08901
214766-78-6
degarelix (inn/usan)
bdbm50102450
ac-d-nal-[d-(pcl)phe]-d-pal-ser-[aph(dhor)]-d-[aph(cbm)]-leu-ilys-pro-dala-nh2
uglypeptide1
sx0xji3a11 ,
fe200486
acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ilys-prolyl-alaninamide
hsdb 7817
n-acetyl-3-(naphtalen-2-yl)-d-alanyl-4-chloro-d-phenylalanyl-3-(pyridin-3-yl)-d-alanyl-l-seryl-4-((((4s)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-l-phenylalanyl-4-(carbamoylamino)-d-phenylalanyl-l-leucyl-n(sup 6)-(1-methylethyl)-l-lysyl-l-prolyl-d
d-alaninamide, n-acetyl-3-(naphtalen-2-yl)-d-alanyl-4-chloro-d-phenylalanyl-3-(pyridin-3-yl)-d-alanyl-l-seryl-4-((((4s)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-l-phenylalanyl-4-(carbamoylamino)-d-phenylalanyl-l-leucyl-n6-(1-methylethyl)-l-lysyl-l
degarelix [usan:inn:ban]
unii-sx0xji3a11
degarelix [who-dd]
degarelix acetate [jan]
degarelix [mart.]
degarelix [inn]
degarelix [usan]
fe-200486 anhydrous free base
degarelix [vandf]
degarelix [hsdb]
degarelix [mi]
fe-200486 (free base)
fe200486 anhydrous free base
degarelix [ema epar]
gtpl5585
HY-16168A
CS-5350
SCHEMBL1397034
AKOS030526717
Q1182795
SCHEMBL21050504
F85338
ac-d-2nal-d-phe(4-cl)-d-3pal-ser-phe(4-s-dihydroorotamido)-d-phe(4-ureido)-leu-lys(ipr)-pro-d-ala-nh2
nsc-771648
nsc771648
DTXSID801026401
AS-82636
n-acetyl-3-(naphtalen-2-yl)-d-alanyl-4-chloro-d-phenylalanyl-3-(pyridin-3-yl)-d-alanyl-l-seryl-4-((((4s)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-l-phenylalanyl-4-(carbamoylamino)-d-phenylalanyl-l-leucyl-n6-(1-methylethyl)-l-lysyl-l-prolyl-d-alani
l02bx02
degarelix (mart.)
degarelixum
GLXC-26186
EN300-20626108

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The hormonal side-effect profiles of the three treatment groups were similar to previously reported effects for androgen-deprivation therapy."( The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.
Andreou, C; Boccon-Gibod, L; Cantor, P; Jensen, JK; Klotz, L; Olesen, TK; Persson, BE; Schröder, FH; Shore, ND, 2008
)
0.35
" Outcomes considered in these analyses included the QT interval by central reading and analysis, and cardiovascular adverse events."( Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer.
Klotz, L; Olesen, TK; Persson, BE; Smith, MR; Wilde, AA, 2010
)
0.36
" Safety and tolerability assessments included adverse events (AEs), physical examinations, electrocardiograms and clinically significant changes in laboratory safety parameters."( Efficacy and safety of androgen deprivation therapy after switching from monthly leuprolide to monthly degarelix in patients with prostate cancer.
Davis, R; de la Rosette, J; Frankel, D; Kold Olesen, T, 2011
)
0.37
"6%) withdrew from the study due to adverse events."( The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre, randomized, maintenance dose-finding phase II study in Japanese patients with prostate cancer.
Akaza, H; Fukuyama, Y; Hoshi, S; Maeda, H; Naito, S; Ohashi, Y; Ozono, S; Takeda, K; Tsukamoto, T; Ueda, T; Yamaguchi, A, 2012
)
0.38
" For safety, adverse events were evaluated."( Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study.
Akaza, H; Akazawa, R; Ito, M; Kusuoka, H; Maeda, H; Naito, S; Nishiyama, T; Ohashi, Y; Ozono, S; Tsukamoto, T; Ueda, T, 2017
)
0.46
" The most frequent adverse event was injection site reaction; however, this did not cause any patient to discontinue treatment."( Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study.
Akaza, H; Akazawa, R; Ito, M; Kusuoka, H; Maeda, H; Naito, S; Nishiyama, T; Ohashi, Y; Ozono, S; Tsukamoto, T; Ueda, T, 2017
)
0.46
" The most common adverse events in the degarelix group were injection site reactions."( Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: A phase III study.
Akaza, H; Akazawa, R; Fukasawa, S; Horie, S; Kusuoka, H; Naito, S; Ohashi, Y; Ozono, S; Saito, M; Tsukamoto, T; Uemura, H; Yokomizo, Y, 2018
)
0.48
" The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months."( Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.
Alexander, JH; Arney, L; Bhatt, DL; Bigelow, R; Clarke, NW; Doyle-Olsen, BT; Evans, CP; Goodman, SG; Higano, CS; Kristensen, H; Lopes, RD; Melloni, C; Nelson, AJ; Nilsson, J; Olesen, TK; Roe, MT; Slovin, SF; Sørensen, PS, 2021
)
0.62
" The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed."( Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.
Alexander, JH; Arney, L; Bhatt, DL; Bigelow, R; Clarke, NW; Doyle-Olsen, BT; Evans, CP; Goodman, SG; Higano, CS; Kristensen, H; Lopes, RD; Melloni, C; Nelson, AJ; Nilsson, J; Olesen, TK; Roe, MT; Slovin, SF; Sørensen, PS, 2021
)
0.62

Pharmacokinetics

ExcerptReferenceRelevance
" The slow absorption half-life was found to be 268 h ( approximately 11 days)."( The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogs.
Agersø, H; Hjortkjaer, R; Karlsson, MO; Knutsson, M; Koechling, W, 2003
)
0.32
"The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone (GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose-concentration dependent absorption."( Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix.
Agersø, H; Jonsson, EN; Madsen, H; Nielsen, HA; Tornøe, CW, 2004
)
0.32
"An integrated semi-mechanistic pharmacodynamic (PD) model describing the relationship between luteinizing hormone (LH) and testosterone (T) after short-term administration of degarelix was developed."( Semi-mechanistic pharmacodynamic modeling for degarelix, a novel gonadotropin releasing hormone (GnRH) blocker.
Agersø, H; Gobburu, JV; Jadhav, PR; Tornøe, CW, 2006
)
0.33
"This review covers the development and introduction of degarelix, its pharmacodynamic and pharmacokinetic properties, and the efficacy and safety results of Phase II and III clinical studies."( Pharmacokinetic and pharmacodynamic profile of degarelix for prostate cancer.
Klotz, L, 2015
)
0.42
"Degarelix has clear pharmacodynamic advantages over the LHRH agonist leuprolide in terms of almost immediate suppression of testosterone to castrate levels and sustained suppression of FSH levels."( Pharmacokinetic and pharmacodynamic profile of degarelix for prostate cancer.
Klotz, L, 2015
)
0.42

Compound-Compound Interactions

ExcerptReferenceRelevance
"This is a single-center, open-label, randomized controlled study that will compare the efficacy and safety of degarelix with those of existing GnRH agonists combined with (125)I-TPPB."( A comparative study on the efficacies of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist in neoadjuvant androgen deprivation therapy combined with transperineal prostate brachytherapy for localized prostate cancer.
Aoki, M; Egawa, S; Kido, M; Miki, K; Sasaki, H; Takahashi, H, 2016
)
0.43
"The objective of this study was to compare the efficacy of abiraterone acetate with that of bicalutamide in combination with gonadotropin-releasing hormone (GnRH) antagonist treatment for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC)."( Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer.
Fujihara, A; Hongo, F; Ito, S; Matsugasumi, T; Ohashi, M; Okihara, K; Shiraishi, T; Ueda, T; Ukimura, O; Yamada, Y, 2021
)
0.62

Bioavailability

ExcerptReferenceRelevance
" The dose-volume effect on the SC release is estimated using a B-spline basis whereas the bioavailability is modeled as a function of the dose-concentration."( Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix.
Agersø, H; Jonsson, EN; Madsen, H; Nielsen, HA; Tornøe, CW, 2004
)
0.32
" The dose-concentration effect on the bioavailability is estimated to decrease at increasing dose-concentrations."( Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix.
Agersø, H; Jonsson, EN; Madsen, H; Nielsen, HA; Tornøe, CW, 2004
)
0.32

Dosage Studied

ExcerptRelevanceReference
") administration to male beagle dogs, and to determine the influence of the different dosing conditions on the absorption profile of degarelix."( The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogs.
Agersø, H; Hjortkjaer, R; Karlsson, MO; Knutsson, M; Koechling, W, 2003
)
0.32
" The dosing conditions varied with respect to route (s."( The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogs.
Agersø, H; Hjortkjaer, R; Karlsson, MO; Knutsson, M; Koechling, W, 2003
)
0.32
" The relative fraction absorbed was found to vary with the concentration of the dosing solution."( The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogs.
Agersø, H; Hjortkjaer, R; Karlsson, MO; Knutsson, M; Koechling, W, 2003
)
0.32
"Through varying the dosing conditions and by applying a joint analysis of all data, the important factors determining the complex absorption of degarelix could be described."( The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogs.
Agersø, H; Hjortkjaer, R; Karlsson, MO; Knutsson, M; Koechling, W, 2003
)
0.32
" The model predicted the time course of LH and T for the second IV and SC dosing studies very well."( Semi-mechanistic pharmacodynamic modeling for degarelix, a novel gonadotropin releasing hormone (GnRH) blocker.
Agersø, H; Gobburu, JV; Jadhav, PR; Tornøe, CW, 2006
)
0.33
"5 ng/ml until the end of the study in 100% of the patients treated with a monthly maintenance dosage of 160 mg of degarelix."( Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer.
de la Rosette, JJ; Jensen, JK; Kold Olesen, T; Persson, BE; Tombal, B; Van Poppel, H, 2008
)
0.35
" Three dosing regimens were evaluated: a starting dose of 240 mg of degarelix subcutaneous (s."( The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.
Andreou, C; Boccon-Gibod, L; Cantor, P; Jensen, JK; Klotz, L; Olesen, TK; Persson, BE; Schröder, FH; Shore, ND, 2008
)
0.35
"5 ng/mL within 3 days of dosing (200 mg, 88%; 240 mg, 92%)."( Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer.
Steinberg, M, 2009
)
0.35
"We investigated associations of baseline cardiovascular disease risk profile, dosing regimen and treatment duration with incident cardiovascular disease events during androgen deprivation therapy with degarelix in patients with prostate cancer."( Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix.
Colli, E; Klotz, L; Smith, MR; Tankó, LB; van der Meulen, E, 2011
)
0.37
"Both monthly degarelix dosing regimens were found to be effective in testosterone suppression without a testosterone surge, prostate-specific antigen reductions and anti-tumour effect in Japanese patients with prostate cancer, as was shown in the overseas Phase III study."( The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre, randomized, maintenance dose-finding phase II study in Japanese patients with prostate cancer.
Akaza, H; Fukuyama, Y; Hoshi, S; Maeda, H; Naito, S; Ohashi, Y; Ozono, S; Takeda, K; Tsukamoto, T; Ueda, T; Yamaguchi, A, 2012
)
0.38
" The main disadvantage of degarelix compared to the LHRH agonists is the monthly dosing and the inconvenience for some patients and practices."( Utility of LHRH antagonists for advanced prostate cancer.
Moul, JW, 2014
)
0.4
"The 3-month dosing regimen of degarelix 360/480 mg was effective and well tolerated for treatment of Japanese prostate cancer patients."( Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study.
Akaza, H; Akazawa, R; Ito, M; Kusuoka, H; Maeda, H; Naito, S; Nishiyama, T; Ohashi, Y; Ozono, S; Tsukamoto, T; Ueda, T, 2017
)
0.46
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
polypeptideA peptide containing ten or more amino acid residues.
[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 (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gonadotropin-releasing hormone receptorHomo sapiens (human)IC50 (µMol)0.00290.00010.12895.2000AID241421; AID266056; AID74279
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gonadotropin-releasing hormone receptorHomo sapiens (human)Kd0.00060.00010.00090.0025AID74429
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (4)

Processvia Protein(s)Taxonomy
gonadotropin secretionGonadotropin-releasing hormone receptorHomo sapiens (human)
cellular response to gonadotropin-releasing hormoneGonadotropin-releasing hormone receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayGonadotropin-releasing hormone receptorHomo sapiens (human)
cellular response to hormone stimulusGonadotropin-releasing hormone receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (2)

Processvia Protein(s)Taxonomy
peptide bindingGonadotropin-releasing hormone receptorHomo sapiens (human)
gonadotropin-releasing hormone receptor activityGonadotropin-releasing hormone receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneGonadotropin-releasing hormone receptorHomo sapiens (human)
membraneGonadotropin-releasing hormone receptorHomo sapiens (human)
plasma membraneGonadotropin-releasing hormone receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (11)

Assay IDTitleYearJournalArticle
AID266056Antagonist activity at human GnRH receptor expressed in HEK293 cells as inhibition of GnRH-induced LH secretion by reporter gene assay2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID104505Compound was tested for inhibition of Leutenizing hormone release at 48 hours (intermediate duration) in castrated male rat assay2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID74429Competitive antagonism of GnRH-induced response in the reporter gene assay2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID74279Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID266063Antiovulatory activity in rat at 2 ug, sc2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
AID241421Antagonism of GnRH response in HEK293 cells expressing human GnRH receptor2005Journal of medicinal chemistry, Jul-28, Volume: 48, Issue:15
Iterative approach to the discovery of novel degarelix analogues: substitutions at positions 3, 7, and 8. Part II.
AID266057Inhibition of GnRH-induced LH secretion in Sprague-Dawley rat at 50 ug, sc for 120 hrs2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
AID266062Histamine release in mast cells by ELISA2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1346002Human GnRH1 receptor (Gonadotrophin-releasing hormone receptors)2010Cancer management and research, Jan-25, Volume: 2Evaluation of degarelix in the management of prostate cancer.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (185)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's37 (20.00)29.6817
2010's107 (57.84)24.3611
2020's41 (22.16)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 9.43

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 weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index9.43 (24.57)
Research Supply Index5.47 (2.92)
Research Growth Index4.90 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (9.43)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials46 (24.21%)5.53%
Reviews39 (20.53%)6.00%
Case Studies10 (5.26%)4.05%
Observational2 (1.05%)0.25%
Other93 (48.95%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]