Moxestrol

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]

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%[1]
Protein binding	Minimal[1]
Metabolism	Liver[2]
Elimination half-life	8.2 hours[1]
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

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

See also: List of estrogens and List of estrogen esters § Ethers of steroidal estrogens

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]