SEGESTERONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H28O3
Molecular Weight	328.4452
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC(=C)[C@](O)(C(C)=O)[C@@]1(C)CC[C@]3([H])[C@@]4([H])CCC(=O)C=C4CC[C@@]23[H]

InChI

InChIKey=SFLXYFZGKSGFKA-XUDSTZEESA-N

InChI=1S/C21H28O3/c1-12-10-19-18-6-4-14-11-15(23)5-7-16(14)17(18)8-9-20(19,3)21(12,24)13(2)22/h11,16-19,24H,1,4-10H2,2-3H3/t16-,17+,18+,19-,20-,21-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11108869 | https://www.ncbi.nlm.nih.gov/pubmed/10361626 | https://www.ncbi.nlm.nih.gov/pubmed/12648180https://www.ncbi.nlm.nih.gov/pubmed/11108869 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf

Segesterone acetate (elcometrine), a progestin, is sold in combination with ethinyl estradiol under the brand name Annovera. Annovera is indicated for use by females of reproductive potential to prevent pregnancy. Segesterone acetate acts as an agonist of the progesterone receptor and it doesn’t possess estrogenic, androgenic, antiandrogenic, or antimineralocorticoid activity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Progesterone receptor 61 Target ID: P06401 Gene ID: 5241.0 Gene Symbol: PGR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11108869	Agonist 2678		56.0 nM [EC50]
Progesterone receptor 61 Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11108869	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Endometriosis 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12648180	Primary	Phase II 1132	Unknown Approved Use Unknown
Pregnancy 65 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10361626	Preventing	Phase III 656	ELMETRIN Approved Use Unknown
pregnancy 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	Preventing	Approved 8429	ANNOVERA Approved Use is indicated for use by females of reproductive potential to prevent pregnancy Launch Date 2018

C_max

Value	Dose	Co-administered	Analyte	Population
294 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1147 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
942.9 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29409834/	200 μg 1 times / day steady-state, vaginal dose: 200 μg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ESTRADIOL	ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3.9 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
15 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
38685.7 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29409834/	200 μg 1 times / day steady-state, vaginal dose: 200 μg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ESTRADIOL	ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
4.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf	0.15 mg 1 times / day steady-state, vaginal dose: 0.15 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: ETHINYL ESTRADIOL	ETHINYL ESTRADIOL	SEGESTERONE ACETATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.15 mg 1 times / day multiple, vaginal Recommended Dose: 0.15 mg, 1 times / day Route: vaginal Route: multiple Dose: 0.15 mg, 1 times / day Co-administed with:: ethinyl estradiol(0.013 mg/day) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf Page: 13	healthy, 18 - 40 years n = 2308 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 2308 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf Page: 13	Disc. AE: Menometrorrhagia, Migraine headache... Other AEs: Migraine headache, Nausea and vomiting... AEs leading to discontinuation/dose reduction: Menometrorrhagia (1.7%) Migraine headache (1.3%) Vulvovaginal mycotic infection (1.3%) Nausea and vomiting (1.2%) Uterine myoma expulsion (1.4%) Other AEs: Migraine headache (38.6%) Nausea and vomiting (25%) Vulvovaginal mycotic infection (14.5%) Abdominal pain lower (13.3%) Dysmenorrhea (12.5%) Vaginal discharge (11.8%) Genitourinary tract infection (10%) Breast discomfort (9.5%) Disorder menstrual (7.5%) Diarrhea (7.2%) Pruritus genital (5.5%) Thrombosis NOS (>= 2 patients) Psychiatric disorder NOS (>= 2 patients) Drug hypersensitivity (>= 2 patients) Abortions spontaneous (>= 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf Page: 13

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767 inducer 389	inhibitor 1852 inducer 97	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882		CYP1A2 701 CYP2B6 547 CYP2C19 293 CYP3A5 76

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2D6 1891	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	unlikely
CYP3A5 130	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 227.0	unlikely

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=70 Page: 70.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209627Orig1s000MultidisciplineR.pdf#page=36 Page: 36.0

Sourcing

Vendor/Aggregator	ID	URL
ChEMBL	CHEMBL2107778
ChemIDplus	7690086	https://chem.nlm.nih.gov/chemidplus/id/0007690086
Compound Cloud	11823650
DrugBank	DB14584	https://www.drugbank.ca/drugs/DB14584
EPA DSSTox	DTXSID00998190	https://comptox.epa.gov/dashboard/DTXSID00998190
KEGG	D10987	http://www.genome.jp/dbget-bin/www_bget?dr:D10987
SureChEMBL	SCHEMBL7053392	https://www.surechembl.org/chemical/SCHEMBL7053392
Wikidata	Q24882947
ZINC	ZINC000033964021	http://zinc15.docking.org/substances/ZINC000033964021

PubMed

Title	Date	PubMed
Use of a single implant of elcometrine (ST-1435), a nonorally active progestin, as a long acting contraceptive for postpartum nursing women.	1999 Feb	10361626
Nestorone: a progestin with a unique pharmacological profile.	2000 Oct-Nov	11108869
Subdermal progestin implant (Nestorone) in the treatment of endometriosis: clinical response to various doses.	2003 Feb	12648180
Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen.	2007 Jun	17519148
Relative progestational and androgenic activity of four progestins used for male hormonal contraception assessed in vitro in relation to their ability to suppress LH secretion in the castrate male rat.	2010 Oct 26	20599585

Patents

Sample Use Guides

In Vivo Use Guide

Elcometrine is delivered within a single subdermal capsule of medical grade polydimethylsiloxane, containing 50 mg of elcometrine. In clinical trials, administration by a vaginal ring was investigated (150 mg of Nestorone and 15 mg of ethinyl estradiol). The development of transdermal gel containing elcometrine is also reported.

Route of Administration: Other

In Vitro Use Guide

Female Sprague–Dawley rats were ovariectomized and 1 week later, injected daily for 3 days with 1 mg 17 b-estradiol (E2) to induce synthesis of PR. The animals were killed on day 4, uteri were collected over dry ice and homogenized. Aliquot of cytosol were incubated overnight at 4°C in glass tubes with [3H]promegestone with or without cold nestorone at different concentrations. The bound and free radioactivity was separated by the dextran-charcoal method.

Name

Type

Language

SEGESTERONE

Official Name

English

17-Hydroxy-16-methylene-19-norpregn-4-ene-3,20-dione

Systematic Name

English

segesterone [INN]

Common Name

English

Segesterone [WHO-DD]

Common Name

English

SEGESTERONE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C776