NOMEGESTROL ACETATE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H30O4
Molecular Weight	370.4819
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC(=O)O[C@@]1(CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@@H]4[C@H]3CC[C@]12C)C(C)=O

InChI

InChIKey=IIVBFTNIGYRNQY-YQLZSBIMSA-N

InChI=1S/C23H30O4/c1-13-11-20-18(17-6-5-16(26)12-19(13)17)7-9-22(4)21(20)8-10-23(22,14(2)24)27-15(3)25/h11-12,17-18,20-21H,5-10H2,1-4H3/t17-,18-,20-,21+,22+,23+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C23H30O4
Molecular Weight	370.4819
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Nomegestrol acetate (NOMAC) is a 19-norprogesterone derivative with high biological activity at the progesterone receptor, a weak anti-androgenic effect, but with no binding to estrogen, glucocorticoid or mineralocorticoid receptors. Nomegestrol has been developed by the Monaco-based company Théramex SAM (a Teva subsidiary). Nomegestrol acetate has been used successfully for the treatment of some gynaecological disorders (menstrual disturbances, dysmenorrhoea, premenstrual syndrome) and as a component of hormone replacement therapy in combination with estradiol for the relief of menopausal symptoms; it has been approved in Europe as monotherapy for the treatment of the menopausal syndrome, uterine diseases and menorrhagia, and in combination with an estrogen for the treatment of menopausal symptoms. Nomegestrol acetate in combination with estradiol is used as an oral contraceptive.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Progesterone receptor 61	Agonist 2,752		4.0 nM [Kd]
Androgen Receptor 169	Antagonist 2,849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pregnancy 65	Preventing		Approved 8,583	ZOELY
Menstrual cycle disorder 5	Primary		Approved 8,583	NOGEST

C_max

Value	Dose	Co-administered	Analyte	Population
6.9 ng/mL	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE plasma	Homo sapiens
6.6 ng/mL	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE plasma	Homo sapiens
12.3 ng/mL	2.5 mg 1 times / day steady-state, oral	ESTRADIOL	NOMEGESTROL ACETATE serum	Homo sapiens
7.19 ng/mL	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE serum	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
96 ng × h/mL	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE plasma	Homo sapiens
106 ng × h/mL	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE plasma	Homo sapiens
106 ng × h/mL	2.5 mg 1 times / day steady-state, oral	ESTRADIOL	NOMEGESTROL ACETATE serum	Homo sapiens
50.4 ng × h/mL	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE serum	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
39.3 h	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE plasma	Homo sapiens
48.1 h	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE plasma	Homo sapiens
45.9 h	2.5 mg 1 times / day steady-state, oral	ESTRADIOL	NOMEGESTROL ACETATE serum	Homo sapiens
41.9 h	2.5 mg single, oral	ESTRADIOL	NOMEGESTROL ACETATE serum	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%			NOMEGESTROL ACETATE serum	Homo sapiens

Doses

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Dose	Population	Adverse events
12.5 mg 1 times / day multiple, oral Highest studied dose\|Higher than recommended	healthy, ADULT
2.5 mg 1 times / day multiple, oral Recommended	healthy, ADULT	Disc. AE: Headaches, Irritability...
55 mg single, subcutaneous Studied dose	healthy, ADULT	Disc. AE: Bleeding, Amenorrhea...

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AEs

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AE	Significance	Dose	Population
Emotional lability	8.3% Disc. AE	2.5 mg 1 times / day multiple, oral Recommended	healthy, ADULT
Headaches	8.3% Disc. AE	2.5 mg 1 times / day multiple, oral Recommended	healthy, ADULT
Irritability	8.3% Disc. AE	2.5 mg 1 times / day multiple, oral Recommended	healthy, ADULT
Nausea	0.17% Disc. AE	55 mg single, subcutaneous Studied dose	healthy, ADULT
Increased blood pressure	0.22% Disc. AE	55 mg single, subcutaneous Studied dose	healthy, ADULT

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

ZOELY (2.5 mg nomegestrol acetate/1.5 mg estradiol) tablets: One tablet is to be taken daily for 28 consecutive days. Each pack starts with 24 white active tablets, followed by 4 yellow placebo tablets. A subsequent pack is started immediately after finishing the previous pack, without a break in daily tablet intake and irrespective of presence or absence of withdrawal bleeding. Withdrawal bleeding usually starts on day 2-3 after intake of the last white tablet and may not have finished before the next pack is started. NOGEST (nomegestrol acetate): the usual dosage is one tablet per day (5 mg/day)

Route of Administration: Oral

In Vitro Use Guide

0.5-50 uM nomegestrol acetate inhibits aromatase activity in a stable aromatase-expressing human breast cancer cell line

Substance Class	Chemical
Record UNII	83J78V5W05
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IOA

Preferred Name

English

NOMEGESTROL ACETATE

Official Name

English

TX-066

Code

English

Nomegestrol acetate [WHO-DD]

Common Name

English

19-NORPREGNA-4,6-DIENE-3,20-DIONE, 17-(ACETYLOXY)-6-METHYL-

Common Name

English

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Classification Tree

Code System

Code

Therapeutic Steroid Hormone

NCI_THESAURUS

C776

REPRODUCTIVE TECHNIQUES

EMA ASSESSMENT REPORTS

ZOELY (AUTHORIZED: CONTRACEPTION)

REPRODUCTIVE TECHNIQUES

EMA ASSESSMENT REPORTS

IOA (WITHDRAWN: CONTRACEPTION)

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Code System

Code

Type

Description

ECHA (EC/EINECS)

261-379-8

PRIMARY

CAS

58652-20-3

PRIMARY

DRUG CENTRAL

1957

PRIMARY

SMS_ID

100000090279

PRIMARY

EPA CompTox

DTXSID90207349

PRIMARY

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Related Record

Type

Details


					EJC4C3UYXH

ANDROGEN RECEPTOR

TARGET -> INHIBITOR

Interaction Type:

BINDING

Qualification:

Ki

Amount:

5.76 NANOMOLAR [2.18 to 9.28] (average)


					DXN1OSB4IB

PROGESTERONE RECEPTOR

TARGET -> AGONIST

Qualification:

Ki

Amount:

3 NANOMOLAR (average)

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Related Record

Type

Details


					W655W625YJ

(2?)-17-(Acetyloxy)-2-hydroxy-6-(hydroxymethyl)-19-norpregna-4,6-diene-3,20-dione

METABOLITE -> PARENT

Amount:


					YLK5RSH57K

(2?)-17-(Acetyloxy)-2-glucoronide-6-methyl-19-norpregna-4,6-diene-3,20-dione

METABOLITE -> PARENT

Qualification:

PLASMA; URINE

Amount:


					YC98W76BX8

17?-Acetoxy-6-hydroxymethyl-3,20-dioxo-19-nor-pregna-4,6-diene

PARENT -> METABOLITE LESS ACTIVE

Comments:

NOMAC was shown to undergo hepatic metabolism via the cytochrome P450 (CYP) system (CYP3A3, 3A4, and 2A6), with hydroxylation to six primary metabolites that have little or no progestational activity.

Amount: