ELAGOLIX

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H30F5N3O5
Molecular Weight	631.5897
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=HEAUOKZIVMZVQL-VWLOTQADSA-N

InChI=1S/C32H30F5N3O5/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)/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 2849		0.9 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain associated with endometriosis 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000Lbl.pdf	Primary		Approved 8583	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 665	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 Health Status: healthy Age Group: 18 –39 years 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	unhealthy, adult (premenopausal women) Health Status: unhealthy Age Group: adult (premenopausal women) Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf	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
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	unhealthy, adult (premenopausal women) Health Status: unhealthy Age Group: adult (premenopausal women) Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf	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

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	substrate 1193 inducer 440 inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 OATP1B1 1079 OATP1B3 961 CYP3A4/5 296 CYP2C19 2057 BCRP 910 CYP1A2 2153 CYP2A6 879 CYP2B6 926 MRP2 499 BSEP 550 OCT1 620 OAT1 725 OAT3 747 OCT2 779 MATE1 415 MATE2 267	CYP3A 220 P-gp 2052 OATP1B1 503 CYP3A4/5 91 CYP2C19 1119 CYP1A2 1197 CYP2A6 626	CYP3A 142 CYP2B6 669 CYP2C8 198 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 145 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	no [IC50 150 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 161 uM]
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=366 Page: 366.0	no [IC50 280 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 45 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	no [IC50 >100 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=366 Page: 366.0	no [IC50 >300 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >29 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >29 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	weak [IC50 >30 uM]
OATP1B1 1095	inhibitor 4027 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 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=367 Page: 367.0	yes [IC50 19 uM]
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=366 Page: 366.0	yes [IC50 36 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes [IC50 4.7 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes [IC50 54 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes [Ki 34 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes [Ki 74 uM]
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=85 Page: 85.0	yes
CYP3A 317	inducer 1966 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 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=364 Page: 364.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
CYP3A4/5 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=41 Page: 41.0	yes
P-gp 2052	substrate 4014 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 220	substrate 4014 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 503	substrate 4014 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 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000MultiD.pdf#page=48 Page: 48.0
hERG 2263	inhibitor 2237 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
BioChemPartner	BCP08827	http://www.biochempartner.com/834153-87-6-BCP08827
BLD Pharm	BD630884	http://www.bldpharm.com/products/834153-87-6.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
CSNpharm	CSN18452	https://www.csnpharm.com/products/elagolix.html
DC Chemicals	DC7407	http://www.dcchemicals.com/product_show-Elagolix_1.html
eNovation Chemicals	D551934	https://www.enovationchem.com/ProductDetails.asp?ProductID=D551934
eNovation Chemicals	Y0973836	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0973836
Excenen	EX-A1765	http://www.excenen.com/searchresultlist.php?id=834153-87-6
iChemical	EBD54911	http://www.ichemical.com/products/834153-87-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
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

PubMed

Title	Date	PubMed
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.	2011-07-28	21657270
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.	2008-12-11	19006286

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

Official Name

English

ELAGOLIX [MI]

Preferred Name

English

elagolix [INN]

Common Name

English

Elagolix [WHO-DD]

Common Name

English

ELAGOLIX [USAN]

Common Name

English

NBI-56418

Code

English

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)BUTANOIC ACID

Systematic 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)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C241