Hexestrol (formerly HSDB2149; HSDB-2149; Cycloestrol; Hexoestrol; Erythrohexestrol; Sinestrol) is a synthetic ER (estrogen receptor) agonist which binds to ERα and ERβ with EC50s of 0.07 nM and 0.175 nM, respectively. It also acts as a microtubule polymerization inhibitor.

Physicochemical Properties

Molecular Formula	C18H22O2
Molecular Weight	270.37
Exact Mass	270.161
CAS #	84-16-2
Related CAS #	(Rac)-Hexestrol-d4;1189950-25-1;(Rac)-Hexestrol-d6;1215476-12-2;(Rac)-Hexestrol-d6 (hexane-2,2,3,4,5,5-d6);1219798-48-7
PubChem CID	192197
Appearance	White to off-white solid powder
Density	1.1±0.1 g/cm3
Boiling Point	399.5±22.0 °C at 760 mmHg
Melting Point	186 °C
Flash Point	181.6±16.9 °C
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.582
LogP	4.98
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	5
Heavy Atom Count	20
Complexity	235
Defined Atom Stereocenter Count	2
SMILES	CC[C@H](C1=CC=C(C=C1)O)[C@@H](CC)C2=CC=C(C=C2)O
InChi Key	PBBGSZCBWVPOOL-HDICACEKSA-N
InChi Code	InChI=1S/C18H22O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,17-20H,3-4H2,1-2H3/t17-,18+
Chemical Name	4-[(3S,4R)-4-(4-hydroxyphenyl)hexan-3-yl]phenol
Synonyms	HSDB 2149; Cycloestrol; Erythrohexestrol; HSDB2149; HSDB-2149;Hexoestrol; Sinestrol
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro activity: Hexestrol binds to ERα with EC50 of 0.07 nM and to ERβ with EC50 of 0.175 nM. Hexestrol inhibits activity of AKR1B13 with IC50 of 3.2 μM. Hexestrol inhibits the d-galactose dehydrogenase activity of thermophilus aldose 1-dehydrogenase with IC50 of 0.063 mM. Hexestrol inhibits the dehydrogenase activity of AKR1C20 towards 10 μM 4-androsten-3α-o1-17-one with IC50 values of 2.7 μM. Hexestrol inhibits 17HSD5 with IC50 of 30 μM, and inhibits TBER1 with IC50 of 0.8 μM. Hexestrol reacts with DNA through the catechol quinone, thus can be a carcinogen.
ln Vivo	At 3 mg/kg, hexestrol (3 and 6 mg/kg; i.p. once daily for 30 days) has no discernible effect on the ovaries of mice[2].
Animal Protocol	Animal/Disease Models: Mus musculus (90-120 days, 25 -50 g)[2] Doses: 3, 6 mg/kg (adopted the same dose used to increase weight gain in cattle) Route of Administration: Ip one time/day for 30 days Experimental Results: Numerous follicles in different stages of development were found at the dose of 3 mg/kg in the ovaries. Not detected the corpora lutea (CL) at the dose of 6 mg/kg.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion ENOUGH MATERIAL CAN BE ABSORBED PERCUTANEOUSLY OR BY RESPIRATORY ROUTE TO PRODUCE...EFFECTS. /ESTROGENS/ STUDIES WITH RADIOACTIVE...HEXESTROL...HAVE CONFIRMED...REPORTS THAT...COMPD ARE RAPIDLY ABSORBED INTO ANIMAL BODY AND...EXCRETED IN FECES AND URINE. PROPORTION EXCRETED...IS...70% IN FECES AND 30% IN URINE... ...TRACES OF...HEXESTROL COULD BE FOUND IN TISSUES 24 HR AFTER...ADMIN TO SHEEP AND GOATS... CONTINUED ADMIN...TO FATTENING STOCK MAY LEAD TO... ACCUMULATION IN EDIBLE PARTS OF CARCASS ALTHOUGH EVIDENCE ON THIS SUBJECT IS CONTROVERSIAL. ESTROGENS USED IN THERAPY ARE, IN GENERAL, READILY ABSORBED THROUGH SKIN, MUCOUS MEMBRANES, & GI TRACT. WHEN THEY ARE APPLIED FOR LOCAL ACTION, ABSORPTION IS OFTEN SUFFICIENT TO CAUSE SYSTEMIC EFFECTS... /ESTROGENS/ Metabolism / Metabolites HEXESTROL YIELDS HEXESTROL-BETA-D-GLUCURONIDE IN RABBIT; JELLINCK PH, BIOCHEM J, 58, 262 (1954). /FROM TABLE/
Toxicity/Toxicokinetics	Interactions EFFECTS OF ESTROGENS CAN BE BLOCKED BY INHIBITORS OF RNA SYNTHESIS (DACTINOMYCIN) OR PROTEIN SYNTHESIS (CYCLOHEXIMIDE). /ESTROGENS/ ESTROGENS...INHIBIT ORAL ANTICOAGULANT ACTIVITY... OTHER INTERACTIONS INCL POTENTIATION OF TRICYCLIC ANTIDEPRESSANT ACTIVITY & REDUCTION OF BOTH PYRIDOXINE & FOLIC ACID LEVELS. PHENOBARBITAL INCR METABOLISM OF ESTROGENS... /ESTROGENS/
References	[1]. The oral use of hexestrol for estrogen deficiency. Am J Obstet Gynecol. 1946 May; 51: 660-5. [2]. Effects of hexestrol on mouse ovarian morphology and ovulation. Maturitas. 2008 Jun 20; 60(2): 153-7. [3]. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997 Mar;138(3):863-70.
Additional Infomation	A synthetic estrogen that has been used as a hormonal antineoplastic agent. Hexestrol is a synthetic hydrogenated derivative of diethylstilbestrol (DES). Hexestrol exhibits strong affinity for estrogen receptors that are overexpressed in some types of cancers. When conjugated with a neoplastic drug, hexestrol may selectively concentrate the cytotoxic agent in estrogen receptor-rich tumors. This agent may also be mutagenic. (NCI04) A synthetic estrogen that has been used as a hormonal antineoplastic agent. See also: Diethylstilbestrol Dipropionate (annotation moved to). Mechanism of Action ...INCR IN SYNTHESIS OF VARIOUS TYPES OF RNA & PROTEIN...STIMULATION OF DNA SYNTHESIS... IT IS NOT CLEAR WHETHER PROMINENT...STIMULATION OF RNA SYNTHESIS IS RESULT OF INCR RNA POLYMERASE ACTIVITY, INCR CHROMATIN TEMPLATE ACTIVITY, ALTERED NUCLEAR TRANSPORT PHENOMENA, OR COMBINATIONS THEREOF. /ESTROGENS/ ...AS RESULT OF...NUCLEAR BINDING...METABOLIC ALTERATIONS ENSUE. ...MRNA & CERTAIN SPECIFIC BUT UNKNOWN PROTEINS ARE APPARENTLY SYNTHESIZED RAPIDLY, PERHAPS BECAUSE OF UNMASKING OF RESTRICTED REGIONS OF DNA. /ESTROGENS/ ESTROGENS ARE LARGELY RESPONSIBLE FOR CHANGES THAT TAKE PLACE @ PUBERTY IN GIRLS, &...FOR TANGIBLE & INTANGIBLE ATTRIBUTES OF FEMININITY. BY DIRECT ACTION, THEY CAUSE GROWTH & DEVELOPMENT OF VAGINA, UTERUS, & FALLOPIAN TUBES. /ESTROGENS/ Therapeutic Uses Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal A SYNTHETIC ESTROGEN. OSTEOPOROSIS...SENILE OSTEOPOROSIS.../&/...POSTMENOPAUSAL OSTEOPOROSIS. ... DEMONSTRATED THAT, AFTER SEVERAL MO OF ESTROGEN REPLACEMENT IN POSTMENOPAUSAL PT, CALCIUM BALANCE BECOMES POSITIVE & PLASMA ALKALINE PHOSPHATASE ACTIVITY & BONE RESORPTION DECR TO NORMAL. /ESTROGENS/ HIRSUTISM. .../IF/ MILD ANDROGENIC INFLUENCE OF OVARIAN...IS SUSPECTED. ... SUPPRESSION OF OVARY WITH ESTROGEN MAY BE WORTHWHILE. ... PREVENTION OF HEART ATTACKS. ...FAVORED POSITION OF WOMEN IN INCIDENCE OF FATAL MYOCARDIAL INFARCTION, ESTROGEN THERAPY HAS BEEN TRIED AS PROPHYLACTIC MEASURE IN MEN. /ESTROGENS/ For more Therapeutic Uses (Complete) data for HEXESTROL (11 total), please visit the HSDB record page. Drug Warnings HEXESTROL IS CONTRAINDICATED DURING PREGNANCY. CONTRAINDICATIONS TO...USE ARE THROMBOEMBOLIC DISORDERS OR PAST HISTORY OF THESE CONDITIONS, MARKEDLY IMPAIRED HEPATIC FUNCTION, KNOWN OR SUSPECTED CARCINOMA OF BREAST OR OTHER ESTROGEN-DEPENDENT NEOPLASIA, & UNDIAGNOSED GENITAL BLEEDING. /ESTROGENS/ IN WOMEN, CHRONIC USE MAY CAUSE SPOTTING OR BREAKTHROUGH VAGINAL BLEEDING; AFTER DISCONTINUATION, WITHDRAWAL BLEEDING USUALLY OCCURS. /ESTROGENS/

Solubility Data

Solubility (In Vitro)

DMSO:42 mg/mL (155.3 mM) Water:<1 mg/mL Ethanol:42 mg/mL (155.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (7.69 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (7.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6986 mL	18.4932 mL	36.9864 mL
	5 mM	0.7397 mL	3.6986 mL	7.3973 mL
	10 mM	0.3699 mL	1.8493 mL	3.6986 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.