ELAGOLIX SODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H29F5N3O5.Na
Molecular Weight	653.5715
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].COC1=CC=CC(=C1F)C2=C(C)N(CC3=C(C=CC=C3F)C(F)(F)F)C(=O)N(C[C@H](NCCCC([O-])=O)C4=CC=CC=C4)C2=O

InChI

InChIKey=DQYGXRQUFSRDCH-UQIIZPHYSA-M

InChI=1S/C32H30F5N3O5.Na/c1-19-28(21-11-6-14-26(45-2)29(21)34)30(43)40(18-25(20-9-4-3-5-10-20)38-16-8-15-27(41)42)31(44)39(19)17-22-23(32(35,36)37)12-7-13-24(22)33;/h3-7,9-14,25,38H,8,15-18H2,1-2H3,(H,41,42);/q;+1/p-1/t25-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210450s000lbl.pdf | https://news.abbvie.com/news/abbvie-receives-us-fda-approval-orilissa-elagolix-for-management-moderate-to-severe-pain-associated-with-endometriosis.htm

Elagolix (ABT-620) is an oral gonadotropin-releasing hormone antagonist being studied for the treatment of endometriosis and uterine fibroids. The U.S. Food and Drug Administration (FDA) approved AbbVie's elagolix under the brand name Orilissa as the first and only oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate to severe endometriosis pain.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 41 Target ID: CHEMBL1855 Sources: https://www.orilissa.com/hcp/about-orilissa/mechanism-of-action \| https://www.ncbi.nlm.nih.gov/pubmed/19006286	Antagonist 2778		0.9 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain associated with endometriosis 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000Lbl.pdf	Primary		Approved 8429	Orilissa Approved Use ORILISSA is a gonadotropin -releasing hormone (GnRH) receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis . Launch Date 2018
Uterine Fibroids 2 Sources: https://clinicaltrials.gov/ct2/show/NCT03271489 https://adisinsight.springer.com/drugs/800020238	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1314 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30570832	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ELAGOLIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3231 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30570832	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ELAGOLIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.48 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30570832	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ELAGOLIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Doses

Dose	Population	Adverse events
400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19033369/	healthy, 18 –39 years n = 5 Health Status: healthy Age Group: 18 –39 years Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/19033369/	Sources: https://pubmed.ncbi.nlm.nih.gov/19033369/
150 mg 1 times / day steady, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: steady Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf Page: p. 143	unhealthy, adult (premenopausal women) n = 475 Health Status: unhealthy Condition: endometriosis Age Group: adult (premenopausal women) Sex: F Population Size: 475 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf Page: p. 143	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (0.8%) Vomiting (0.6%) Headache (0.8%) Depression (0.4%) Hot flush (0.8%) Insomnia (0.4%) Irritability (0.4%) Mood swings (0.4%) Abdominal pain (0.2%) Acne (0.2%) Endometriosis (0.4%) Migraine (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf Page: p. 143
200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf Page: p. 143	unhealthy, adult (premenopausal women) n = 477 Health Status: unhealthy Condition: endometriosis Age Group: adult (premenopausal women) Sex: F Population Size: 477 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf Page: p. 143	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (1.5%) Vomiting (0.4%) Headache (1%) Depression (0.6%) Hot flush (2.5%) Insomnia (0.4%) Irritability (0.4%) Mood swings (0.2%) Abdominal pain (0.4%) Acne (0.4%) Facial swelling (0.4%) Migraine (0.4%) Depressed mood (0.4%) Diarrhea (0.6%) ALT increased (0.4%) AST increased (0.4%) Arthralgia (0.6%) Rash (0.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf Page: p. 143

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587	substrate 1037 inducer 389 inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 OATP1B1 788 OATP1B3 706 CYP3A4/5 278 CYP2C19 1478 BCRP 699 CYP1A2 1524 CYP2A6 707 CYP2B6 810 MRP2 383 BSEP 402 OCT1 512 OAT1 599 OAT3 642 OCT2 647 MATE1 306 MATE2 263	CYP3A 191 P-gp 1537 OATP1B1 406 CYP3A4/5 85 CYP2C19 991 CYP1A2 1054 CYP2A6 543	CYP3A 129 CYP2B6 547 CYP2C8 168 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 145 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	no [IC50 150 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 161 uM]
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=366 Page: 366.0	no [IC50 280 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 45 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 >100 uM]
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=366 Page: 366.0	no [IC50 >300 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >29 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >29 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes [IC50 1.7 uM]	yes (co-administration study) Comment: BCRP/OATP1B1 inhibition by elagolix 300 mg BID ↓AUC by 40% ↔ Cmax (rosuvastatin) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	yes [IC50 19 uM]
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=366 Page: 366.0	yes [IC50 36 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes [IC50 4.7 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes [IC50 54 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes [Ki 34 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes [Ki 74 uM]
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes	yes (co-administration study) Comment: CYP3A4 induction by elagolix 150 mg QD and 300 mg BID ↓AUC by 35 - 55% ↓Cmax by 19 – 44% (midazolam) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes	likely (co-administration study) Comment: CYP3A4/P-gp induction by rifampin, 600 mg QD ↑Cmax by 100% ↑AUC by 65% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes	yes (co-administration study) Comment: CYP3A4 inhibition by ketoconazole, 400 mg QD ↑Cmax by 77% ↑AUC by 120% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes	yes (co-administration study) Comment: OATP1B1 inhibition by a single dose of rifampin, 600 mg ↑Cmax by 337% ↑AUC by 458% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=48 Page: 48.0
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=48 Page: 48.0		NBI‐61692 2

Sourcing

Vendor/Aggregator	ID	URL
Achemtek	0102-013369	http://www.achemtek.com/834153-87-6
Ambeed	A645801	https://www.ambeed.com/products/834153-87-6.html
Aurum Pharmatech LLC	Z-3253	http://www.Aurumpharmatech.com/Product/ProductDetails/Z_3253
BLD Pharm	BD630884	http://www.bldpharm.com/products/834153-87-6.html
BioChemPartner	BCP08827	http://www.biochempartner.com/834153-87-6-BCP08827
CSNpharm	CSN18452	https://www.csnpharm.com/products/elagolix.html
Chem Scene	CS-5329	http://www.chemscene.com/834153-87-6.html
ChemFish Tokyo co.,ltd	11250647	http://www.chemfish.co.jp/index.php?id=4607&project=product
ChemMol	49418581	http://www.chemmol.com/chemmol/49418581.html
Chemspace	CSSB00161189399	https://chem-space.com/CSSB00161189399
DC Chemicals	DC7407	http://www.dcchemicals.com/product_show-Elagolix_1.html
Excenen	EX-A1765	http://www.excenen.com/searchresultlist.php?id=834153-87-6
J&W PharmLab	99R0002	https://www.jwpharmlab.com/home/product/99R0002
Lab Network	LN01346224	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01346224
MedChem Express	HY-14789	https://www.medchemexpress.com/Elagolix.html
MuseChem	I005006	https://www.musechem.com/product/I005006.html
OChem	27611	http://www.ocheminc.com/index.php?act=psearch&pid=153E876
Smolecule	S526963	http://www.smolecule.com/products/s526963
Synblock Inc	SB16700	http://www.synblock.com/product/834153-87-6.html
THE BioTek	bt-267303	https://www.thebiotek.com/product/inhibitors/bt-267303
THE BioTek	bt-345829	https://www.thebiotek.com/product/others/bt-345829
eNovation Chemicals	D551934	https://www.enovationchem.com/ProductDetails.asp?ProductID=D551934
eNovation Chemicals	Y0973836	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0973836
iChemical	EBD54911	http://www.ichemical.com/products/834153-87-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor.	2008 Dec 11	19006286
Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor.	2011 Jul 28	21657270

Patents

Sample Use Guides

In Vivo Use Guide

Normal liver function or mild hepatic impairment : 150 mg once daily for up to 24 months or 200 mg twice daily for up to 6 months. (2.1) Moderate hepatic impairment: 150 mg once daily for up to 6 months. (2.1) Oral tablets: 150 mg and 200 mg

Route of Administration: Oral

In Vitro Use Guide

Elagolix displays high affinity in a competition binding assay for hGnRH-R (Ki = 0.90 nM) and low CYP3A4 inhibition (IC50 = 56 uM). It is a slowly disassociating antagonist exhibiting very high affinity (KD = 54 pM) and insurmountable antagonism. Elagolix is highly selective at hGnRH-R, its wider receptor selectivity is tested at a concentration of 10 uM in a panel of radioligand binding assays for 100 off-target receptors, ion channels, enzymes, and transporters, and significant activity is not observed (inhibition <50%). It does not stimulate histamine release from cultured rat peritoneal mast cells.

Name

Type

Language

ELAGOLIX SODIUM

Official Name

English

ORIAHNN COMPONENT ELAGOLIX SODIUM

Brand Name

English

BUTANOIC ACID, 4-(((1R)-2-(5-(2-FLUORO-3-METHOXYPHENYL)-3-((2-FLUORO-6-(TRIFLUOROMETHYL)PHENYL)METHYL)-3,6-DIHYDRO-4-METHYL-2,6-DIOXO-1(2H)-PYRIMIDINYL)-1- PHENYLETHYL)AMINO)-, MONOSODIUM SALT

Common Name

English

ELAGOLIX SODIUM COMPONENT OF ORIAHNN

Brand Name

English

ELAGOLIX SODIUM [ORANGE BOOK]

Common Name

English

SODIUM 4-(((1R)-2-(5-(2-FLUORO-3-METHOXYPHENYL)-3-((2-FLUORO-6- (TRIFLUOROMETHYL)PHENYL)METHYL)-4-METHYL-2,6-DIOXO-3,6-DIHYDROPYRIMIDIN-1(2H)-YL)-1- PHENYLETHYL)AMINO)BUTANOATE

Systematic Name

English

ORLISSA

Brand Name

English

ELAGOLIX SODIUM SALT [MI]

Common Name

English

NBI-56418-NA

Code

English

Elagolix sodium [WHO-DD]

Common Name

English

ELAGOLIX SODIUM [USAN]

Common Name

English

NBI-56418 NA

Code

English

Code System Code Type Description

SMS_ID

100000174591