Moxestrol

Moxestrol
Clinical data
Trade names	Surestryl
Other names	R-2858, RU-2858, NSC-118191; 11β-Methoxy-17α-ethynylestradiol; 11β-MeO-EE 11β-Methoxy-17α-ethynylestra-1,3,5(10)-triene-3,17β-diol
Pregnancy; category	X (Contraindicated);
Routes of; administration	By mouth
Drug class	Estrogen; Estrogen ether
ATC code	G03CB04 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	33%
Protein binding	Minimal
Metabolism	Liver
Elimination half-life	8.2 hours
Identifiers
	IUPAC name (8S,9S,11S,13S,14S,17R)-17-ethynyl-11-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol;
CAS Number	34816-55-2;
PubChem CID	11954041;
ChemSpider	10128336;
UNII	6923NT44OW;
KEGG	C14757;
ChEBI	CHEBI:34857;
ChEMBL	ChEMBL1628161;
CompTox Dashboard (EPA)	DTXSID8022375 ;
Chemical and physical data
Formula	C21H26O3
Molar mass	326.436 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC12CC(C3C(C1CCC2(C#C)O)CCC4=C3C=CC(=C4)O)OC;
	InChI InChI=1S/C21H26O3/c1-4-21(23)10-9-17-16-7-5-13-11-14(22)6-8-15(13)19(16)18(24-3)12-20(17,21)2/h1,6,8,11,16-19,22-23H,5,7,9-10,12H2,2-3H3/t16-,17-,18-,19+,20-,21-/m0/s1; Key:MTMZZIPTQITGCY-OLGWUGKESA-N;

Moxestrol, sold under the brand name Surestryl, is an estrogen medication which has been used in Europe for the treatment of menopausal symptoms and menstrual disorders.^[3]^[4]^[2]^[5]^[6] It is taken by mouth.^[6] In addition to its use as a medication, moxestrol has been used in scientific research as a radioligand of the estrogen receptor.^[7]

Medical uses

Moxestrol is or has been used in the treatment of menopausal symptoms and menstrual disorders.^[2]^[6] It has been used at dosages of 50 to 150 μg per week for long-term therapy to 25 to 250 μg per day for short-term therapy.^[6]

Pharmacology

Pharmacodynamics

Moxestrol is an estrogen, or an agonist of the estrogen receptors.^[2]^[5] It is the 11β-methoxy derivative of ethinylestradiol and is one of the most potent estrogens known, being some 10 to 100 times more potent than estradiol and about 5-fold more potent than ethinylestradiol.^[2]^[5] The very high potency of moxestrol has been attributed to its high affinity for the estrogen receptor (ER), its negligible plasma binding to sex hormone binding globulin and low binding to serum albumin,^[1] and its lower relative rate of metabolism.^[2]^[5] In contrast to estradiol, which has roughly the same affinity for both ERs (K_i = 0.12 nM and 0.15 nM, respectively), moxestrol possesses several-fold selectivity for the ERα (K_i = 0.50 nM) over ERβ (K_i = 2.6 nM).^[8]

Relative affinities (%) of moxestrol and related steroids
Compound	PRTooltip Progesterone receptor	ARTooltip Androgen receptor	ERTooltip Estrogen receptor	GRTooltip Glucocorticoid receptor	MRTooltip Mineralocorticoid receptor	SHBGTooltip Sex hormone-binding globulin	CBGTooltip Corticosteroid binding globulin
Estradiol	2.6	7.9	100	0.6	0.13	8.7	<0.1
Ethinylestradiol	15–25	1–3	112	1–3	<1	?	?
Moxestrol (11β-MeO-EE)	0.8	<0.1	12	3.2	<0.1	<0.2	<0.1
RU-16117 (11α-MeO-EE)	1–3	<1	13	<1	<1	?	?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PRTooltip progesterone receptor, testosterone for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Sources: ^[9]^[10]^[11]^[12]

Pharmacokinetics

The bioavailability of moxestrol is 33%.^[1] Its plasma protein binding is minimal.^[1] The medication is metabolized in the liver.^[2] Its biological half-life is 8.2 hours.^[1]

Chemistry

Moxestrol, also known as 11β-methoxy-17α-ethynylestradiol (11β-MeO-EE) or as 11β-methoxy-17α-ethynylestra-1,3,5(10)-triene-3,17β-diol, is a synthetic estrane steroid and a derivative of estradiol.^[3] It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methoxy group at the C11β position and a derivative of 11β-methoxyestradiol with an ethynyl group at the C17α position.^[3] The compound is the C11β isomer or C11 epimer of RU-16117 (11α-methoxy-17α-ethynylestradiol.^[13]

Society and culture

Generic names

Moxestrol is the generic name of the drug and its INNTooltip International Nonproprietary Name.^[3]^[4] It is also known by its developmental code name R-2858 or RU-2858.^[3]^[4]

Brand names

Moxestrol is or has been marketed under the brand name Surestryl.^[3]^[4]

Availability

Moxestrol is or has been marketed in Europe.^[2]

References

^ ^a ^b ^c ^d ^e ^f ^g Salmon J, Coussediere D, Cousty C, Raynaud JP (August 1983). "Pharmacokinetics and metabolism of moxestrol in animals--rat, dog and monkey". Journal of Steroid Biochemistry. 19 (2): 1223–1234. doi:10.1016/0022-4731(83)90421-1. PMID 6887930.
^ ^a ^b ^c ^d ^e ^f ^g ^h Li JJ, Nandi S, Li SA (6 December 2012). Hormonal Carcinogenesis: Proceedings of the First International Symposium. Springer Science & Business Media. pp. 184–. ISBN 978-1-4613-9208-8.
^ ^a ^b ^c ^d ^e ^f Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 841–. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c ^d Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 186–. ISBN 978-0-7514-0499-9.
^ ^a ^b ^c ^d Nunn AD (19 June 1992). Radiopharmaceuticals: Chemistry and Pharmacology. CRC Press. pp. 342–. ISBN 978-0-8247-8624-3.
^ ^a ^b ^c ^d William Martindale; Royal Pharmaceutical Society of Great Britain. Dept. of Pharmaceutical Sciences (1993). The Extra Pharmacopoeia. Pharmaceutical Press. p. 1188. ISBN 978-0-85369-300-0. Moxestrol is a synthetic oestrogen with actions and uses similar to thosre described for the oestrogens in general. Moxestrol is reponed to have a prolonged duration of action. It has been given by mouth in the treatment of menopausal, postmenopausal, and menstrual symptoms. Dose have ranged from 50 to 100 μg weekly for long-term therapy to 25 to 250 μg daily for short-term use.
^ Raynaud JP, Martin PM, Bouton MM, Ojasoo T (September 1978). "11beta-Methoxy-17-ethynyl-1,3,5(10)-estratriene-3,17beta-diol (moxestrol), a tag for estrogen receptor binding sites in human tissues". Cancer Research. 38 (9): 3044–3050. PMID 679210.
^ Lund TD, Hinds LR, Handa RJ (February 2006). "The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus". The Journal of Neuroscience. 26 (5): 1448–1456. doi:10.1523/JNEUROSCI.3777-05.2006. PMC 6675494. PMID 16452668.
^ Raynaud JP, Ojasoo T, Bouton MM, Philibert D (1979). "Receptor Binding as a Tool in the Development of New Bioactive Steroids". Drug Design. Medicinal Chemistry: A Series of Monographs. Vol. 11. Academic Press. pp. 169–214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9781483216102.
^ Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies". Cancer Research. 38 (11 Pt 2): 4186–4198. PMID 359134.
^ Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". Journal of Steroid Biochemistry. 27 (1–3): 255–269. doi:10.1016/0022-4731(87)90317-7. PMID 3695484.
^ Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, et al. (January 1980). "Steroid hormone receptors and pharmacology". Journal of Steroid Biochemistry. 12: 143–157. doi:10.1016/0022-4731(80)90264-2. PMID 7421203.
^ Kaye AM, Kaye M (22 October 2013). Development of Responsiveness to Steroid Hormones: Advances in the Biosciences. Elsevier Science. pp. 61–. ISBN 978-1-4831-5308-7.

[SalmonCoussediere1983-1] ^ ^a ^b ^c ^d ^e ^f ^g Salmon J, Coussediere D, Cousty C, Raynaud JP (August 1983). "Pharmacokinetics and metabolism of moxestrol in animals--rat, dog and monkey". Journal of Steroid Biochemistry. 19 (2): 1223–1234. doi:10.1016/0022-4731(83)90421-1. PMID 6887930.

[LiNandi2012-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h Li JJ, Nandi S, Li SA (6 December 2012). Hormonal Carcinogenesis: Proceedings of the First International Symposium. Springer Science & Business Media. pp. 184–. ISBN 978-1-4613-9208-8.

[Elks2014-3] ^ ^a ^b ^c ^d ^e ^f Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 841–. ISBN 978-1-4757-2085-3.

[MortonHall1999-4] Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 186–. ISBN 978-0-7514-0499-9.

[Nunn1992-5] Nunn AD (19 June 1992). Radiopharmaceuticals: Chemistry and Pharmacology. CRC Press. pp. 342–. ISBN 978-0-8247-8624-3.

[MartindaleSciences1993-6] William Martindale; Royal Pharmaceutical Society of Great Britain. Dept. of Pharmaceutical Sciences (1993). The Extra Pharmacopoeia. Pharmaceutical Press. p. 1188. ISBN 978-0-85369-300-0. Moxestrol is a synthetic oestrogen with actions and uses similar to thosre described for the oestrogens in general. Moxestrol is reponed to have a prolonged duration of action. It has been given by mouth in the treatment of menopausal, postmenopausal, and menstrual symptoms. Dose have ranged from 50 to 100 μg weekly for long-term therapy to 25 to 250 μg daily for short-term use.

[pmid679210-7] Raynaud JP, Martin PM, Bouton MM, Ojasoo T (September 1978). "11beta-Methoxy-17-ethynyl-1,3,5(10)-estratriene-3,17beta-diol (moxestrol), a tag for estrogen receptor binding sites in human tissues". Cancer Research. 38 (9): 3044–3050. PMID 679210.

[pmid16452668-8] Lund TD, Hinds LR, Handa RJ (February 2006). "The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus". The Journal of Neuroscience. 26 (5): 1448–1456. doi:10.1523/JNEUROSCI.3777-05.2006. PMC 6675494. PMID 16452668.

[RaynaudOjasoo1979-9] Raynaud JP, Ojasoo T, Bouton MM, Philibert D (1979). "Receptor Binding as a Tool in the Development of New Bioactive Steroids". Drug Design. Medicinal Chemistry: A Series of Monographs. Vol. 11. Academic Press. pp. 169–214. doi:10.1016/B978-0-12-060308-4.50010-X. ISBN 9781483216102.

[pmid359134-10] Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies". Cancer Research. 38 (11 Pt 2): 4186–4198. PMID 359134.

[pmid3695484-11] Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". Journal of Steroid Biochemistry. 27 (1–3): 255–269. doi:10.1016/0022-4731(87)90317-7. PMID 3695484.

[pmid7421203-12] Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, et al. (January 1980). "Steroid hormone receptors and pharmacology". Journal of Steroid Biochemistry. 12: 143–157. doi:10.1016/0022-4731(80)90264-2. PMID 7421203.

[KayeKaye2013-13] Kaye AM, Kaye M (22 October 2013). Development of Responsiveness to Steroid Hormones: Advances in the Biosciences. Elsevier Science. pp. 61–. ISBN 978-1-4831-5308-7.

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