NOMEGESTROL

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@](O)(C(C)=O)[C@@]1(C)CC[C@]3([H])[C@@]4([H])CCC(=O)C=C4C(C)=C[C@@]23[H]

InChI

InChIKey=KZUIYQJTUIACIG-YBZCJVABSA-N

InChI=1S/C21H28O3/c1-12-10-18-16(15-5-4-14(23)11-17(12)15)6-8-20(3)19(18)7-9-21(20,24)13(2)22/h10-11,15-16,18-19,24H,4-9H2,1-3H3/t15-,16-,18-,19+,20+,21+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://adis.springer.com/drugs/800010246
Curator's Comment: Description was created based on several sources, including http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001213/WC500115831.pdf | https://www.ncbi.nlm.nih.gov/pubmed/20329803 | https://www.ncbi.nlm.nih.gov/pubmed/22364709

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 Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8049131 \| https://www.ncbi.nlm.nih.gov/pubmed/21757063	Agonist 2678		4.0 nM [Kd]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21757063	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pregnancy 65 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001213/WC500115831.pdf	Preventing		Approved 8429	ZOELY Approved Use ZOELY is used for oral contraception. Launch Date 2011
Menstrual cycle disorder 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20329803	Primary		Approved 8429	NOGEST Approved Use NOGEST (nomegestrol acetate) is used: In women before menopause: for the treatment of menstrual cycle disorders caused by the absence or low secretion of progesterone. These troubles of the menstrual cycle can be: - Menstrual cycle length abnormalities, - Bleeding abnormalities during or outside menstruation, - Painful menstruation, - Troubles before menstruation such as nervousness or irritability (premenstrual syndrome), - Breast tenderness. In post menopausal women: as Hormone Replacement Therapy (HRT) for the treatment of menopause disorders in addition with a treatment containing estrogen in non-hysterectomized women with at least 6 months since their last natural period.

PubMed

Title	Date	PubMed
Reversal effects of nomegestrol acetate on multidrug resistance in adriamycin-resistant MCF7 breast cancer cell line.	2001	11434876
Implant contraception.	2001 Dec	11727176
[HRT in post-menopausal women: endometrial histology and bleeding patterns].	2002 Aug	12114870
Effects of transdermal hormone replacement therapy on levels of soluble P- and E-selectin in postmenopausal healthy women.	2002 Mar	11872198
In-vivo angiogenesis and progestogens.	2002 Mar	11870137
Classification and pharmacology of progestins.	2003 Dec 10	14670641
Newer progestogens.	2003 Jan	12626173
Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy.	2003 Jul 25	12818462
[Comparison of changes in biochemical markers of bone turnover after 6 months of hormone replacement therapy with either transdermal 17 beta-estradiol or equine conjugated estrogen plus nomegestrol acetate].	2003 May	14567121
[Nome gesrol (lutenyl) induced severe acute hepatitis].	2004 Jan	15041823
Serum leptin levels and body composition in postmenopausal women: effects of hormone therapy.	2004 Jul-Aug	15243285
Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period.	2005 Jun	16096169
Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.	2007 Jan-Feb	17075432
[Evaluation of the hematochemical parameters and bone mineral density of women in physiological menopause treated with hormone replacement therapy with nomegestrol acetate and surgical menopause treated with estrogen replacement. Part II].	2007 Jun	17576400
Longitudinal evaluation of serum leptin and bone mineral density in early postmenopausal women.	2007 May-Jun	17242633
Effects of hormone treatment on hemostasis variables.	2007 Oct	17882670
Insulin resistance in postmenopausal women: concurrent effects of hormone replacement therapy and coffee.	2008 Oct	18781481
Classification and pharmacology of progestins.	2008 Sep-Oct	19434889

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

Name

Type

Language

NOMEGESTROL

Official Name

English

nomegestrol [INN]

Common Name

English

17-hydroxy-6-methyl-19-norpregna-4,6-diene-3,20-dione [EP IMPURITY]

Common Name

English

17-HYDROXY-6-METHYL-19-NOR-4,6-PREGNADIENE-3,20-DIONE

Common Name

English

Nomegestrol [WHO-DD]

Common Name

English

NOMEGESTROL [USAN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QG03FB12