DEGARELIX

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C82H103ClN18O16
Molecular Weight	1632.259
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CCCN1C(=O)[C@H](CCCCNC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CC=C(NC(N)=O)C=C2)NC(=O)[C@H](CC3=CC=C(NC(=O)[C@@H]4CC(=O)NC(=O)N4)C=C3)NC(=O)[C@H](CO)NC(=O)[C@@H](CC5=CN=CC=C5)NC(=O)[C@@H](CC6=CC=C(Cl)C=C6)NC(=O)[C@@H](CC7=CC=C8C=CC=CC8=C7)NC(C)=O)C(=O)N[C@H](C)C(N)=O

InChI

InChIKey=MEUCPCLKGZSHTA-XYAYPHGZSA-N

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

HIDE SMILES / InChI

Description
Sources: https://firmagon.com | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022201s011lbl.pdf

DEGARELIX (FIRMAGON®) is a synthetic linear decapeptide amide containing seven unnatural amino acids, five of which are D-amino acids. It is a GnRH receptor antagonist. It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone. DEGARELIX (FIRMAGON®) is effective in achieving and maintaining testosterone suppression below the castration level of 50 ng/dL and is indicated for the treatment of patients with advanced prostate cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 41 Target ID: CHEMBL1855 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16759096	Antagonist 2778		0.58 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced prostate cancer 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022201s011lbl.pdf	Primary		Approved 8429	FIRMAGON Approved Use FIRMAGON is a GnRH receptor antagonist indicated for treatment of patients with advanced prostate cancer. Launch Date 2008

C_max

Value	Dose	Co-administered	Analyte	Population
66 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/26513436/	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.2 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022201s016lbl.pdf	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
635 ng × day/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/26513436/	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1054 ng × day/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022201s016lbl.pdf	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
43 day REVIEW https://pubmed.ncbi.nlm.nih.gov/26513436/	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
53 day DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022201s016lbl.pdf	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% REVIEW https://pubmed.ncbi.nlm.nih.gov/26513436/	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022201s016lbl.pdf	240 mg single, subcutaneous dose: 240 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		DEGARELIX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
240 mg 1 times / 4 weeks multiple, subcutaneous Recommended Dose: 240 mg, 1 times / 4 weeks Route: subcutaneous Route: multiple Dose: 240 mg, 1 times / 4 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22457321 Page: p.482	unhealthy, 74.2 n = 137 Health Status: unhealthy Condition: Advanced prostate cancer Age Group: 74.2 Sex: M Population Size: 137 Sources: https://pubmed.ncbi.nlm.nih.gov/22457321 Page: p.482	Disc. AE: Injection site induration, Malaise... AEs leading to discontinuation/dose reduction: Injection site induration (2.19%) Malaise (1.46%) Hepatic function abnormal (1.46%) Sources: https://pubmed.ncbi.nlm.nih.gov/22457321 Page: p.482
240 mg 1 times / 4 weeks multiple, subcutaneous Recommended Dose: 240 mg, 1 times / 4 weeks Route: subcutaneous Route: multiple Dose: 240 mg, 1 times / 4 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022201lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Advanced prostate cancer Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022201lbl.pdf Page: p.1	Disc. AE: QT interval prolonged... AEs leading to discontinuation/dose reduction: QT interval prolonged Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022201lbl.pdf Page: p.1
10 mg single, subcutaneous Dose: 10 mg Route: subcutaneous Route: single Dose: 10 mg Sources: https://clinicaltrials.gov/ct2/show/NCT00947882	unhealthy n = 101 Health Status: unhealthy Condition: Lower Urinary Tract Symptoms Population Size: 101 Sources: https://clinicaltrials.gov/ct2/show/NCT00947882	Other AEs: Sick sinus syndrome, Ileus... Other AEs: Sick sinus syndrome (serious, 1 patient) Ileus (serious, 1 patient) Subileus (serious, 1 patient) Abscess intestinal (serious, 1 patient) Contusion (serious, 1 patient) Osteoarthritis (serious, 1 patient) Adenosquamous cell carcinoma (serious, 1 patient) Prostate cancer (serious, 1 patient) Carotid sinus syndrome (serious, 1 patient) Cerebrovascular accident (serious, 1 patient) Pulmonary embolism (serious, 1 patient) Respiratory failure (serious, 1 patient) Deep vein thrombosis (serious, 1 patient) Injection site erythema (below serious, 11 patient) Injection site pain (below serious, 2 patients) Injection site induration (below serious, 6 patients) Nasopharyngitis (below serious, 7 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00947882
20 mg single, subcutaneous Dose: 20 mg Route: subcutaneous Route: single Dose: 20 mg Sources: https://clinicaltrials.gov/ct2/show/NCT00947882	unhealthy n = 100 Health Status: unhealthy Condition: Lower Urinary Tract Symptoms Population Size: 100 Sources: https://clinicaltrials.gov/ct2/show/NCT00947882	Other AEs: Clostridium difficile colitis, Intervertebral disc protrusion... Other AEs: Clostridium difficile colitis (serious, 1 patient) Intervertebral disc protrusion (serious, 1 patient) Injection site erythema (below serious, 14 patients) Injection site pain (below serious, 10 patients) Injection site induration (below serious, 7 patients) Hot flush (below serious, 4 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00947882
30 mg single, subcutaneous Dose: 30 mg Route: subcutaneous Route: single Dose: 30 mg Sources: https://clinicaltrials.gov/ct2/show/NCT00947882	unhealthy n = 105 Health Status: unhealthy Condition: Lower Urinary Tract Symptoms Population Size: 105 Sources: https://clinicaltrials.gov/ct2/show/NCT00947882	Other AEs: Atrioventricular block complete, Intervertebral disc protrusion... Other AEs: Atrioventricular block complete (serious, 1 patient) Intervertebral disc protrusion (serious, 1 patient) Osteoarthritis (serious, 1 patient) Colon cancer metastatic (serious, 1 patient) Depression (serious, 1 patient) Chronic obstructive pulmonary disease (serious, 1 patient) Hypertension (serious, 1 patient) Injection site erythema (below serious, 18 patients) Injection site pain (below serious, 18 patients) Injection site induration (below serious, 11 patient) Hypertension (below serious, 9 patients) Hot flush (below serious, 8 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00947882

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inducer 389 inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP3A4/5 278 CYP2C19 1478 CYP2E1 882 P-gp 1461 OATP1B3 706 BCRP 699 MRP2 383 BSEP 402 OATP1B1 788 OATP2B1 123	CYP450 65 P-gp 1537 BCRP 561 MRP2 205 BSEP 52 OATP1B1 406 OATP2B1 104	CYP1A2 701 CYP2C8 168 CYP2C19 293 BCRP 75 MRP2 111 BSEP 6 OATP1B1 26 OATP2B1 6

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
BSEP 403	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=33 Page: 33.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=33 Page: 33.0	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=33 Page: 33.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=33 Page: 33.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=33 Page: 33.0	no
MRP2 475	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP1B1 803	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP2B1 126	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP2B1 126	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	unlikely
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	unlikely
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	unlikely
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	unlikely
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	unlikely
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 10 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP2B1 104	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=34 Page: 34.0	no
CYP450 65	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_ClinPharmR.pdf#page=33 Page: 33.0	poor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022201s000_PharmR_P1.pdf#page=38 Page: 38.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00BF3V	https://www.aablocks.com/goods/Goods/detail?id=AA00BF3V
Achemtek	0102-014289	http://www.achemtek.com/214766-78-6
Adooq BioScience	A12840	https://www.adooq.com/degarelix-acetate.html
Alsachim	2920	http://www.alsachim.com/product-C3990-glo.bal-view.html
Aurum Pharmatech LLC	Z-3147	http://www.Aurumpharmatech.com/Product/ProductDetails/Z_3147
BOC Sciences	214766-78-6	https://www.bocsci.com/degarelix-acetate-cas-214766-78-6-item-465293.html
CSNpharm	CSN18109	https://www.csnpharm.com/products/degarelix.html
Chem Scene	CS-5350	http://www.chemscene.com/214766-78-6.html
ChemMol	49400009	http://www.chemmol.com/chemmol/49400009.html
Chemenu	CM100964	http://www.chemenu.com/products/CM100964
Chemspace	CSSB00161189522	https://chem-space.com/CSSB00161189522
Glentham Life Sciences	GP2084	http://www.glentham.com/products/product/GP2084/
Lab Network	LN01345459	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01345459
MedChem Express	HY-16168A	https://www.medchemexpress.com/Degarelix.html
MolPort	MolPort-046-417-128	https://www.molport.com/shop/molecule-link/MolPort-046-417-128
MuseChem	I002648	https://www.musechem.com/product/I002648.html
OChem	25795	http://www.ocheminc.com/index.php?act=psearch&pid=766D786
Renno Tech	RL02641	http://www.rennotech.com/product_show.asp?id=2890
eNovation Chemicals	D320201	https://www.enovationchem.com/ProductDetails.asp?ProductID=D320201
iChemical	EBD29766	http://www.ichemical.com/chemicals/cas-214766-78-6

PubMed

Title	Date	PubMed
Evaluation of degarelix in the management of prostate cancer.	2010 Jan 25	21188095

Patents

Sample Use Guides

In Vivo Use Guide

FIRMAGON® is for subcutaneous administration only: Treatment is started with a dose of 240 mg given as two injections of 120 mg each. The starting dose is followed by maintenance doses of 80 mg administered as a single injection every 28 days.

Route of Administration: Other

Name

Type

Language

DEGARELIX

Official Name

English

FE200486 ANHYDROUS FREE BASE

Code

English

FE-200486 ANHYDROUS FREE BASE

Code

English

DEGARELIX [USAN]

Common Name

English

DEGARELIX [HSDB]

Common Name

English

DEGARELIX [MART.]

Common Name

English

DEGARELIX [VANDF]

Common Name

English

DEGARELIX ACETATE [JAN]

Common Name

English

Degarelix [WHO-DD]

Common Name

English

degarelix [INN]

Common Name

English

DEGARELIX [EMA EPAR]

Common Name

English

FE-200486 (FREE BASE)

Code

English

DEGARELIX [MI]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

FIRMAGON (AUTHORIZED: PROSTATIC NEOPLASMS)