(4R)-N-{4-[(2S)-2-{[(1R)-2-[4-(carbamoylamino)phenyl]-1-{[(1S)-1-{[(2S)-1-(2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl)-1-oxo-6-[(propan-2-yl)amino]hexan-2-yl]carbamoyl}-3-methylbutyl]carbamoyl}ethyl]carbamoyl}-2-[(2S)-2-[(2R)-2-[(2R)-3-(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-hydroxypropanamido]ethyl]phenyl}-2,6-dioxo-1,3-diazinane-4-carboxamide

• ChemBase ID: 4437
• Molecular Formular: C82H103ClN18O16
• Molecular Mass: 1632.25922
• Monoisotopic Mass: 1630.74879699
• SMILES: Clc1ccc(C[C@@H](NC(=O)[C@H](NC(=O)C)Cc2cc3c(cc2)cccc3)C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N2C(CCC2)C(=O)N[C@H](C)C(=O)N)CCCCNC(C)C)CC(C)C)Cc2ccc(NC(=O)N)cc2)Cc2ccc(NC(=O)[C@@H]3NC(=O)NC(=O)C3)cc2)CO)Cc2cccnc2)cc1
• Canonical SMILES: OC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCCC1C(=O)N[C@@H](C(=O)N)C)CCCCNC(C)C)CC(C)C)Cc1ccc(cc1)NC(=O)N)Cc1ccc(cc1)NC(=O)[C@H]1CC(=O)NC(=O)N1)NC(=O)[C@H](NC(=O)[C@H](NC(=O)[C@@H](Cc1ccc2c(c1)cccc2)NC(=O)C)Cc1ccc(cc1)Cl)Cc1cccnc1
• InChI: InChI=1S/C82H103ClN18O16/c1-45(2)35-60(72(107)92-59(16-9-10-33-87-46(3)4)80(115)101-34-12-17-68(101)79(114)88-47(5)70(84)105)93-74(109)63(38-51-23-30-58(31-24-51)91-81(85)116)95-76(111)64(39-50-21-28-57(29-22-50)90-71(106)66-42-69(104)100-82(117)99-66)97-78(113)67(44-102)98-77(112)65(41-53-13-11-32-86-43-53)96-75(110)62(37-49-19-26-56(83)27-20-49)94-73(108)61(89-48(6)103)40-52-18-25-54-14-7-8-15-55(54)36-52/h7-8,11,13-15,18-32,36,43,45-47,59-68,87,102H,9-10,12,16-17,33-35,37-42,44H2,1-6H3,(H2,84,105)(H,88,114)(H,89,103)(H,90,106)(H,92,107)(H,93,109)(H,94,108)(H,95,111)(H,96,110)(H,97,113)(H,98,112)(H3,85,91,116)(H2,99,100,104,117)/t47-,59+,60+,61-,62-,63-,64+,65-,66-,67+,68?/m1/s1
• InChIKey: MEUCPCLKGZSHTA-RHCWOGDZSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (4R)-N-{4-[(2S)-2-{[(1R)-2-[4-(carbamoylamino)phenyl]-1-{[(1S)-1-{[(2S)-1-(2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl)-1-oxo-6-[(propan-2-yl)amino]hexan-2-yl]carbamoyl}-3-methylbutyl]carbamoyl}ethyl]carbamoyl}-2-[(2S)-2-[(2R)-2-[(2R)-3-(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-hydroxypropanamido]ethyl]phenyl}-2,6-dioxo-1,3-diazinane-4-carboxamide
• IUPAC Traditional name: (4R)-N-{4-[(2S)-2-{[(1R)-2-[4-(carbamoylamino)phenyl]-1-{[(1S)-1-{[(2S)-1-(2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl)-6-(isopropylamino)-1-oxohexan-2-yl]carbamoyl}-3-methylbutyl]carbamoyl}ethyl]carbamoyl}-2-[(2S)-2-[(2R)-2-[(2R)-3-(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-hydroxypropanamido]ethyl]phenyl}-2,6-dioxo-1,3-diazinane-4-carboxamide
• Brand Name: Firmagon
• Synonyms: Degarelix

Database IDs

• CAS Number: 214766-78-6
• PubChem SID: 99443253; 160967869
• PubChem CID: 44151801

CALCULATED PROPERTIES

JChem

• Acid pKa: 7.230074
• H Acceptors: 18
• H Donor: 17
• LogD (pH = 5.5): -2.5750062
• LogD (pH = 7.4): -1.6150687
• Log P: -1.4164691
• Molar Refractivity: 431.128 cm^3
• Polarizability: 167.52441 Å^3
• Polar Surface Area: 512.87 Å^2
• Rotatable Bonds: 41
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 2.66
• LOG S: -5.6
• Solubility (Water): 4.10e-03 g/l

DETAILS

DrugBank - DB06699

• Drug Groups: approved
• Description: Degarelix is used for the treatment of advanced prostate cancer. Degarelix is a synthetic peptide derivative drug which binds to gonadotropin-releasing hormone(GnRH) receptors in the pituitary gland and blocks their interaction with GnRH. This antagonism reduces luteinising hormone (LH), follicle-stimulating hormone (FSH) and in turn, testosterone suppression. Reduction in testosterone is important in treating men with advanced prostate cancer.
• Indication: Degaralix is used for the management of advanced prostate cancer. Its action ultimately results in a reduction in circulating androgens, which provides a therapeutic benefit by reducing the growth stimulus used by hormone-sensitive malignant prostate tissue.
• Pharmacology: Degarelix is a synthetic derivative of GnRH decapeptide which normally stimulates the GnRH receptor. Gonadotropin and androgen production result from the binding of endogenous GnRH to the GnRH receptor. The ability of Degarelix to antagonize GnRH at its receptor and suppress the release of these hormones is what gives it potency in slowing advanced prostate cancer. ; Degarelix antagonizes the GnRH receptor which in turn blocks the release of LH and FSH from the pituitary. The reduction in LH leads to a decrease in testosterone release from the testes and subsequently reduces the size and growth of the prostate cancer.
• Affected Organisms: Humans and other mammals
• Biotransformation: Degarelix is subject to peptide hydrolysis during its passage through the hepatobiliary system and is mainly excreted as peptide fragments in feces. Approximately 20-30% of a given dose of degarelix is renally eliminated, suggesting that approximately 70-80% is excreted via the hepatobiliary system.
• Absorption: Degarelix forms a depot at the site of injection after subcutaneous administration from which the drug slowly released into circulation. Peak plasma concentrations of degarelix generally occur within 2 days following subcutaneous administration of a single 240-mg dose at a concentration of 40 mg/mL.
• Half Life: 23-61 days
• Protein Binding: 90% of the drug is bound to plasma proteins.
• References: Steinberg M: Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther. 2009;31 Pt 2:2312-31. [Pubmed] ; Persson BE, Kold Olesen T, Jensen JK: Degarelix: a new approach for the treatment of prostate cancer. Neuroendocrinology. 2009;90(3):235-44. Epub 2009 Jul 14. [Pubmed]
• External Links: Wikipedia

REFERENCES

• Steinberg M: Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther. 2009;31 Pt 2:2312-31. Pubmed
• Persson BE, Kold Olesen T, Jensen JK: Degarelix: a new approach for the treatment of prostate cancer. Neuroendocrinology. 2009;90(3):235-44. Epub 2009 Jul 14. Pubmed