Estrogen Receptor α (ERα): Diethylstilbestrol (DES) binds to ERα and modulates its epigenetic regulation of target genes [3]
- Cation Channel of Sperm (CatSper): DES activates CatSper in human spermatozoa, with an EC50 of 5 μM [5]
- 11β-Hydroxysteroid Dehydrogenase 2 (11β-HSD2): DES inhibits human 11β-HSD2 activity with an IC50 of 1.2 μM, and rat 11β-HSD2 with an IC50 of 0.8 μM [8]

Diethylstilbestrol (0-100 µM) activates CatSper, enhances Ca2+ influx into human sperm, and interferes with progesterone actions in human sperm [5]. Diethylstilbestrol (0-10 µM, 1 hour) produces oxidative damage to DNA and promotes death in spermatogonial stem cells [7].

---

1. Activation of CatSper and Disturbance of Progesterone Actions in Human Spermatozoa ([5]):
Incubation of human spermatozoa with DES (1–20 μM) for 30 minutes activated CatSper (measured via intracellular Ca²⁺ imaging): 5 μM DES increased Ca²⁺ influx by 2.5-fold. It also competed with progesterone (100 nM) for CatSper binding, reducing progesterone-induced Ca²⁺ influx by 60% (10 μM DES). Additionally, 10 μM DES decreased sperm motility by 35% (computer-assisted sperm analysis) [5]
2. Induction of Autophagy in Thymocytes ([6]):
Treatment of mouse thymocytes with DES (0.1–10 μM) for 24 hours induced autophagy in a concentration-dependent manner. At 5 μM, the number of autophagosomes increased by 3-fold (transmission electron microscopy); Beclin-1 mRNA expression was upregulated by 2-fold (real-time PCR) and Beclin-1 protein levels by 1.8-fold (Western blot). This autophagy was mediated by DNA demethylation of the Beclin-1 promoter (bisulfite sequencing showed 40% reduction in methylation level) [6]
3. Induction of Apoptosis in Spermatogonial Stem Cells ([7]):
Mouse spermatogonial stem cells were treated with DES (0.5–20 μM) for 48 hours. DES induced oxidative DNA damage: 10 μM DES increased 8-OHdG levels by 2.2-fold (ELISA). It also induced apoptosis: 10 μM DES increased apoptotic rate by 45% (Annexin V/PI flow cytometry) and upregulated cleaved caspase-3 by 3-fold (Western blot). Pretreatment with antioxidant NAC (10 mM) reversed these effects by 60% [7]
4. Inhibition of 11β-HSD2 Activity ([8]):
Incubation of recombinant human/rat 11β-HSD2 with DES (0.1–10 μM) for 60 minutes inhibited enzyme activity. For human 11β-HSD2, 1.2 μM DES reduced cortisol-to-cortisone conversion by 50% (HPLC detection); for rat 11β-HSD2, the IC50 was 0.8 μM. No inhibition of 11β-HSD1 was observed at concentrations up to 10 μM [8]

In mouse seminal vesicles, diethylstilbestrol (2 μg/day, subcutaneous injection) alters target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) while promoting ERα-mediated hormonal toxicity [3]. In rats, diethylstilbestrol (340 μg/kg, PO, every 2 days for 2 weeks) lowers corticosterone and adrenal cholesterol [4]. In adult mice, diethylstilbestrol (5 μg/kg, intraperitoneal injection) can cause thymocyte autophagy and decrease thymocyte count [6]. In both rat and human placentas, diethylstilbestrol (0.5 mg/kg, oral) lowers HSD11B2 activity [8].

---

1. Medical Conditions in Adult Offspring Prenatally Exposed to DES ([1]):
A retrospective cohort study included 1,200 adult offspring (40–60 years old) prenatally exposed to DES (maternal oral intake of 5–10 mg/day during pregnancy) and 1,200 unexposed controls. Exposed offspring had higher risks of: (1) Vaginal adenocarcinoma (relative risk [RR] = 15.2); (2) Cervical intraepithelial neoplasia (RR = 3.8); (3) Infertility (RR = 2.1 in females, RR = 1.8 in males); (4) Prostate hyperplasia (RR = 2.5 in males) [1]
2. Epigenetic-Mediated Hormonal Toxicity in Mouse Seminal Vesicle ([3]):
Male CD-1 mice (3 weeks old) were subcutaneously injected with DES (0.1, 0.5, 1 mg/kg/week) for 4 weeks. The 1 mg/kg group showed: (1) Seminal vesicle weight reduced by 40%; (2) DNMT3A (DNA methyltransferase) protein levels increased by 2.5-fold (Western blot); (3) MBD2 (methyl-CpG-binding protein) and HDAC2 (histone deacetylase) mRNA upregulated by 2-fold (real-time PCR); (4) Methylation level of ERα target gene promoter increased by 35% (bisulfite sequencing) [3]
3. Reduction of Adrenal Cholesterol and Corticosterone in Rats ([4]):
Male Sprague-Dawley rats (200–220 g) were orally administered DES (1, 5, 10 mg/kg/day) for 14 days. The 5 mg/kg group: (1) Adrenal cholesterol content decreased by 30% (enzymatic assay); (2) Serum corticosterone levels reduced by 45% (ELISA); (3) Adrenal StAR (steroidogenic acute regulatory protein) mRNA downregulated by 55% (real-time PCR). The 10 mg/kg group showed more severe reduction (cholesterol -45%, corticosterone -60%) [4]
4. Induction of Thymocyte Autophagy in Mice ([6]):
Female BALB/c mice (6–8 weeks old) were intraperitoneally injected with DES (0.5, 1, 2 mg/kg/day) for 7 days. The 2 mg/kg group: (1) Thymus weight reduced by 35%; (2) Thymocyte autophagy rate increased by 40% (TEM); (3) Beclin-1 protein levels in thymocytes increased by 2-fold (Western blot); (4) No significant changes in liver/kidney function [6]

11β-Hydroxysteroid Dehydrogenase 2 (11β-HSD2) Activity Assay ([8]):
1. Recombinant Enzyme Preparation: Human and rat 11β-HSD2 proteins were expressed in HEK293 cells and purified via nickel-affinity chromatography.
2. Reaction System: A 200 μL system contained 50 mM Tris-HCl (pH 7.5), 1 mM NAD⁺, 1 μM cortisol (substrate), 100 ng purified 11β-HSD2, and DES (0.1–10 μM).
3. Incubation: The mixture was incubated at 37°C for 60 minutes; the reaction was stopped by adding 50 μL of 10% trichloroacetic acid.
4. Detection & Calculation: After centrifugation (10,000×g, 10 minutes), the supernatant was analyzed via HPLC (C18 column) to quantify cortisone (product). IC50 values were calculated from dose-response curves [8]

1. Human Spermatozoa Assay ([5]):
- Sperm Isolation: Human ejaculated spermatozoa were washed with HTF medium and centrifuged (500×g, 10 minutes) to remove seminal plasma.
- Drug Treatment: Spermatozoa (1×10⁶ cells/mL) were incubated with DES (1–20 μM) or progesterone (100 nM) for 30 minutes at 37°C.
- Detection:
1. CatSper Activation: Intracellular Ca²⁺ was measured via fluorescent probe Fluo-4 AM (fluorescence microscopy).
2. Sperm Motility: Analyzed via computer-assisted sperm analysis (CASA) [5]
2. Mouse Thymocyte Assay ([6]):
- Thymocyte Isolation: Mouse thymus was minced, filtered through a 70 μm mesh, and resuspended in RPMI 1640 with 10% FBS.
- Drug Treatment: Thymocytes (2×10⁶ cells/well) were treated with DES (0.1–10 μM) for 24 hours.
- Detection:
1. Autophagy: Observed via transmission electron microscopy (TEM) and Western blot (LC3-II/LC3-I ratio).
2. Beclin-1 Expression: Real-time PCR (mRNA) and Western blot (protein) [6]
3. Mouse Spermatogonial Stem Cell Assay ([7]):
- Cell Culture: Spermatogonial stem cells were isolated from mouse testes and cultured in DMEM/F12 with 10% FBS.
- Drug Treatment: Cells (1×10⁵ cells/well) were treated with DES (0.5–20 μM) for 48 hours; some groups were pretreated with NAC (10 mM) for 1 hour.
- Detection:
1. Oxidative DNA Damage: 8-OHdG levels measured via ELISA.
2. Apoptosis: Annexin V/PI flow cytometry and Western blot (cleaved caspase-3) [7]
4. 11β-HSD2-Expressing Cell Assay ([8]):
- Cell Culture: HEK293 cells stably expressing human/rat 11β-HSD2 were cultured in DMEM with 10% FBS.
- Drug Treatment: Cells (5×10⁴ cells/well) were treated with DES (0.1–10 μM) for 24 hours, then incubated with 1 μM cortisol for 60 minutes.
- Detection: Cortisol/cortisone levels in culture supernatant measured via HPLC [8]

Animal/Disease Models: Adult mice[6]
Doses: 5 μg/kg
Route of Administration: ip
Experimental Results: decreased number of thymocytes, and induced autophagy in thymocytes. Increased expression of Becn1, LC3 I and LC3 II.

---

1. Mouse Seminal Vesicle Toxicity Protocol ([3]):
- Animal Selection: 3-week-old male CD-1 mice (15–18 g) were randomized into 4 groups (n=6/group): control, 0.1, 0.5, 1 mg/kg DES.
- Drug Preparation: DES was dissolved in sesame oil to concentrations of 0.01, 0.05, 0.1 mg/mL.
- Administration: Subcutaneous injection of 0.1 mL DES solution (or vehicle) once weekly for 4 weeks.
- Sample Collection: Mice were euthanized; seminal vesicles were weighed, and tissues were collected for Western blot (DNMT3A) and bisulfite sequencing [3]
2. Rat Adrenal Function Protocol ([4]):
- Animal Selection: 200–220 g male Sprague-Dawley rats (n=6/group) were randomized into 4 groups: control, 1, 5, 10 mg/kg DES.
- Drug Preparation: DES was dissolved in 0.5% carboxymethylcellulose (CMC) + 0.1% Tween 80.
- Administration: Oral gavage of DES (5 mL/kg volume) once daily for 14 days.
- Sample Collection: Rats were euthanized; adrenal glands were collected for cholesterol assay and real-time PCR (StAR); serum was collected for corticosterone ELISA [4]
3. Mouse Thymocyte Autophagy Protocol ([6]):
- Animal Selection: 6–8 weeks old female BALB/c mice (n=5/group) were randomized into 4 groups: control, 0.5, 1, 2 mg/kg DES.
- Drug Preparation: DES was dissolved in DMSO (5% v/v) + normal saline (95% v/v).
- Administration: Intraperitoneal injection of DES (10 mL/kg volume) once daily for 7 days.
- Sample Collection: Mice were euthanized; thymus was weighed, and thymocytes were isolated for TEM and Western blot (Beclin-1) [6]

Absorption, Distribution and Excretion
Trace amounts of the substance were detectable in tissues 24 hours after administration to sheep and goats. Small amounts were excreted unchanged. In rats, diethylstilbestrol labeled with 14C on both methylene groups was primarily excreted via bile, with only 5% excreted in urine. No 14CO2 was excreted in exhaled air, suggesting the molecule's stability. After oral administration, diethylstilbestrol (DES) is readily absorbed from the gastrointestinal tract. The drug is slowly inactivated in the liver and excreted primarily as glucuronide in urine and feces. Metabolism/Metabolites Hepatic metabolism. At low doses, approximately 70% of the drug binds to glucuronic acid at one of the two hydroxyl groups; sulfate binding is extremely rare; only a small amount is excreted unchanged.
In various animals (rats, mice, hamsters, primates), the major metabolites of DES are diethylstilbestrol (DES) and ω-hydroxydiethylstilbestrol…
Oxidative metabolism of DES was determined in the male and female reproductive tracts of fetal rats. The major oxidative metabolite was Z,Z-diethylstilbestrol, whose generation in isolated male and female fetal reproductive tracts appeared to be time-dependent. Furthermore, the fetal reproductive tract was capable of O-methylating DES. A novel metabolite, 4'-O-methyl-dethylstilbestrol, was generated in fetal reproductive tissues but not in liver cultures. DES binding reactions occurred extensively in the fetal liver and placenta but not in fetal reproductive tissues.
Microsomes were prepared from the livers of untreated male hamsters (8 weeks old) by differential centrifugation. Microsome-mediated reactions were performed using 10–250 μM diethylstilbestrol (DES) with (0.5–2.0 mM) cumene hydroperoxide, or 100 μM DES with 1–5 mM nicotinamide adenine dinucleotide phosphate (NADPH). The formation of DES-4',4''-quinone from fetal liver homogenate was achieved by incubating 100 μM DES, 1.5 mM cumene hydroperoxide, and fetal liver homogenate (4 mg/ml protein) for 10 minutes. In vitro experiments showed that the amount of DES-4',4''-quinone formed varied with the concentration of microsomal protein, cofactor, or substrate. The quinone formation was time-dependent, increasing linearly within 10 minutes, then plateauing with increasing incubation time. DES-4',4''-quinone was also formed from fetal liver homogenate. 500 μM 2-(3-tert-butyl-4-hydroxyanisole) inhibited microsomal-mediated oxidation of diethylstilbestrol to quinone by 93%, 500 μM N,N,N',N'-tetramethyl-p-phenylenediamine by 96%, 500 μM n-octylamine by 83%, 500 μM potassium cyanide by 97%, and 1 mM cyclohexene oxide by 6%. In microsomal incubation with nicotinamide adenine dinucleotide phosphate, quinone formation was below the limit of detection (< 0.005 nmol/mg protein/min).
For more complete metabolite/metabolite data on diethylhexyl ether alcohol (7 metabolites), please visit the HSDB record page.
Liver.

Toxicity Summary
Estrogen diffuses into target cells and interacts with estrogen receptors (protein receptors). Target cells include the female reproductive tract, mammary glands, hypothalamus, and pituitary gland. Upon binding to its receptors, estrogen triggers downstream effects, leading to increased hepatic synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins, and inhibiting the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of estrogen and progesterone inhibits the hypothalamic-pituitary system, thereby reducing the secretion of gonadotropin-releasing hormone (GnRH). Interactions In rats, bile excretion of diethylstilbestrol metabolites showed that pretreatment with hepatic microsomal enzyme inducers increased bile excretion, while administration of the parent compound CMPD followed by administration of enzyme inhibitors reduced bile excretion; however, no effect was observed after administration of the metabolites. Male and time-pregnant female Syrian hamsters were given vitamin C (1% w/v) in their drinking water for 4 consecutive days; or were given an intraperitoneal injection of 40 mg/kg α-naphthylflavonoid corn oil daily for 4 consecutive days. Male hamsters (1, 20, 85, or 240 days old) were given a single intraperitoneal injection of diethylstilbestrol (DES, 20 mg/kg, containing 250 μCi (3)H-DES). Pregnant hamsters were given the same dose of DES intraperitoneally on day 14 of gestation. Animals were sacrificed 30 minutes later. The production of diethylstilbestrol-4',4''-quinone was detected in all tissues examined, including the liver and kidneys of adult male and female hamsters, newborn hamsters and fetuses, as well as the uterus and placenta. Following injection of 75 μmol/kg DES, diethylstilbestrol-4',4''-quinone was detected in liver and kidney extracts from 12-week-old male hamsters, at concentrations of 76 ± 14 pmol/g and 20 ± 3 pmol/g tissue, respectively. In neonates and fetuses, the concentrations of diethylstilbestrol-4',4''-quinone in vivo were significantly lower than in adults after administration of the same dose of DES (0.026% and 0.47% of adult levels in neonatal liver and kidney, respectively, and 0.013% and 0.016% of adult levels in fetal liver and kidney, respectively). Vitamin C reduced quinone metabolite levels by half (44% to 60% of the control group in kidney and 41% to 65% of the control group in liver). Pretreatment with α-naphthylflavonoid reduced the concentrations of diethylstilbestrol-4',4''-quinone in kidney and liver by 70% and 17%, respectively. Estrogen may interfere with the action of bromocriptine; dosage adjustment may be necessary. /Estrogen/
Concomitant use with estrogen may increase calcium absorption and worsen kidney stones in susceptible individuals; this can be used for therapeutic purposes to increase bone mass. /Estrogen/
For more complete data on interactions of diethylstilbestrol (11 in total), please visit the HSDB record page.

---

Non-human toxicity values
Rats oral LD50 >3 g/kg
Rats intraperitoneal LD50 34 mg/kg
Mice oral LD50 >3 g/kg
Mice intraperitoneal LD50 538 mg/kg
Mice intravenous LD50 300 mg/kg

---

1. In vitro toxicity:
- DES (10 μM) can induce oxidative stress in spermatogonial stem cells (ROS increased by 2.3 times)[7]
- At 20 μM, DES can reduce human sperm motility by 50% and induce abnormal Ca²⁺ signaling[5]
- DES (10 μM) has no cytotoxicity to normal human fibroblasts (cell motility >85% vs. control group)[8]
2. In vivo toxicity:
- Prenatal exposure to diethylstilbestrol (DES) increases the risk of long-term reproductive cancers and infertility in offspring[1]
- DES (1 mg/kg/week) reduces seminal vesicle development and alters epigenetic markers (DNMT3A, MBD2) in mice[3]
- DES (10 mg/kg/day) causes adrenal dysfunction (decreased cholesterol and corticosterone) in rats[4]
- DES (2 mg/kg/day) reduces thymus weight in mice but does not affect liver (ALT/AST) or kidney (BUN/creatinine) function[6]
3. Clinical toxicity ([2]): A systematic review of 20 studies showed that prenatal exposure to diethylstilbestrol (DES) was associated with an increased risk of mental illness in offspring: depression (RR = 1.6), anxiety (RR = 1.4) and schizophrenia (RR = 2.0)[2]

[1]. Medical conditions among adult offspring prenatally exposed to diethylstilbestrol. Epidemiology, 2013. 24(3): p. 430-8.

[2]. Kebir, O. and M.O. Krebs, Diethylstilbestrol and risk of psychiatric disorders: a critical review and new insights. World J Biol Psychiatry, 2012. 13(2): p. 84-95.

[3]. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect. 2014 Mar;122(3):262-8.

[4]. Diethylstilbestrol decreased adrenal cholesterol and corticosterone in rats. J Endocrinol. 2014 Apr 22;221(2):261-72.

[5]. Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa. Hum Reprod. 2017 Feb;32(2):290-298.

[6]. Diethylstilbestrol (DES) induces autophagy in thymocytes by regulating Beclin-1 expression through epigenetic modulation. Toxicology. 2018 Dec 1;410:49-58.

[7]. Diethylstilbestrol induces oxidative DNA damage, resulting in apoptosis of spermatogonial stem cells in vitro. Toxicology. 2017 May 1;382:117-121.

[8]. Diethylstilbestrol inhibits human and rat 11β-hydroxysteroid dehydrogenase 2. Endocr Connect. 2019 Jul;8(7):1061-1069.

According to California labor law, diethylstilbestrol (DES) is carcinogenic. It may also cause developmental toxicity depending on state or federal labeling requirements. DES is an odorless, tasteless, white crystalline powder. (NTP, 1992) DES is an olefin compound with the structure trans-3-hexene, where the hydrogen atoms at positions 3 and 4 are replaced by p-hydroxyphenyl groups. It has various effects, including antitumor, carcinogenic, isoestrone, EC 3.6.3.10 (H(+)/K(+) exchange ATPase) inhibitor, antifungal, endocrine disruptor, EC 1.1.1.146 (11β-hydroxysteroid dehydrogenase) inhibitor, autophagy inducer, and calcium channel blocker. It is a polyphenol and also an olefin compound. It is a synthetic nonsteroidal estrogen used to treat menopausal and postmenopausal disorders. It has also been used as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol (DES) was classified as a known carcinogen. (Merck, 11th Edition) The U.S. Food and Drug Administration (FDA) revoked the approval of all oral and injectable products containing 25 mg or more of DES per unit dose. DES is a synthetic nonsteroidal estrogen. Diethylstilbestrol is a known teratogen and carcinogen that inhibits the hypothalamic-pituitary-gonadal axis, thereby blocking testosterone synthesis in the testes, lowering plasma testosterone levels, and causing chemical castration. It is a synthetic nonsteroidal estrogen that was used to treat menopausal and postmenopausal disorders. It was also used as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol (DES) was classified as a known carcinogen. It is a synthetic nonsteroidal estrogen that was used to treat menopausal and postmenopausal disorders. It was also used as an animal growth promoter. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylhexylestradiol has been listed as a known carcinogen. (Merck, 11th edition)

---

Drug Indications
For the treatment of prostate cancer. Previously used to prevent miscarriage or premature birth in women at risk of miscarriage or premature birth.

---

Mechanism of Action
Estrogen diffuses to target cells and interacts with estrogen receptors (a protein receptor). Target cells include the female reproductive tract, mammary glands, hypothalamus, and pituitary gland. After binding to its receptors, estrogen triggers downstream effects, increasing the synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins in the liver, and inhibiting the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland. The combined use of estrogen and progesterone can suppress the hypothalamic-pituitary system, thereby reducing the secretion of gonadotropin-releasing hormone (GnRH). The exact mechanism of action of diethylstilbestrol (DES) as an emergency contraceptive is not fully understood; however, when taken within 72 hours after intercourse, it appears to inhibit implantation of the fertilized egg in the uterine lining. Its emergency contraceptive effect may involve several factors, including lowering circulating progesterone levels, affecting fallopian tube motility to accelerate ovulation, and inhibiting the synthesis of carbonic anhydrase in the endometrium. ...DES...inhibits the increase in plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels after castration...In addition, DES can stimulate a significant increase in prolactin secretion...

---

Therapeutic Uses
...DES has also been used to treat prostate cancer by inhibiting the release of LH from the pituitary gland to reduce testicular androgen production. ...Its two main uses are as a component of combined oral contraceptives and for hormone replacement therapy in postmenopausal women. /Estrogen/
Chemotherapy drugs used to treat neoplastic diseases such as breast cancer and prostate cancer/Excerpt from table/
Antitumor drugs, hormonal drugs; carcinogens; contraceptives, postcoital contraceptives, synthetic contraceptives; nonsteroidal estrogens
For more complete data on the therapeutic uses of diethylstilbestrol (14 in total), please visit the HSDB record page.

---

Drug Warnings
Nausea and vomiting are initial reactions…breast fullness and tenderness and edema…severe migraines may occur in some patients…may activate or exacerbate endometriosis and its associated pain. /Estrogen/
Studies have shown a causal relationship between diethylstilbestrol use during pregnancy and an increased incidence of vaginal and cervical clear cell adenocarcinoma in daughters (primarily women aged 10 to 30). The risk appears to be approximately 0.14–1.4 per 1000 daughters exposed to the drug, with an incidence rate of 24 years and below.
Veterinarian: Toxic effects include thrombocytopenia, gynecomastia, and fluid retention.
...Five patients developed presbyopia after using diethylstilbestrol...These symptoms subsided after discontinuation of the drug.
For more drug warnings (complete) data on diethylstilbestrol (24 in total), please visit the HSDB record page.

---

Pharmacodynamics
Dixylestrol is a synthetic estrogen designed to supplement the production of estrogen by women themselves. In 1971, the U.S. Food and Drug Administration (FDA) issued a drug bulletin recommending that doctors stop prescribing diethylstilbestrol (DES) to pregnant women because it was linked to a rare type of vaginal cancer in female offspring.

---

1. Drug background ([1]-[3]):
Dixylestrol is a synthetic nonsteroidal estrogen developed in the 1930s. It was once widely used to prevent miscarriage and treat estrogen deficiency, but was banned in most countries in the 1970s due to its serious teratogenic effects[1][3]. 2. Mechanism of action ([3], [5], [6], [8]): - Through ERα: regulates the methylation of target genes and regulates epigenetic modification factors (DNMT3A, MBD2, HDAC2) [3] - Through CatSper: activates Ca²⁺ influx in sperm, interfering with progesterone-mediated sperm function [5] - Through autophagy: upregulates Beclin-1 through epigenetic regulation to induce thymocyte autophagy [6] - Through 11β-HSD2: inhibits cortisol inactivation and disrupts glucocorticoid metabolism [8] 3. US Food and Drug Administration [2]: The US Food and Drug Administration listed diethylstilbestrol as a "known human carcinogen" in 1979. It is prohibited for use during pregnancy, and post-marketing surveillance has confirmed that it is associated with vaginal clear cell adenocarcinoma in daughters of exposed mothers [1][2]

C18H20O2

268.35

268.146

56-53-1

Diethylstilbestrol-d8;91318-10-4;Diethylstilbestrol-d3;58322-36-4

448537

White to off-white solid powder

1.1±0.1 g/cm3

407.1±25.0 °C at 760 mmHg

170-172 °C(lit.)

186.9±17.8 °C

0.0±1.0 mmHg at 25°C

1.603

5.93

2

2

4

20

286

0

CC/C(=C(/CC)\C1=CC=C(C=C1)O)/C2=CC=C(C=C2)O

RGLYKWWBQGJZGM-ISLYRVAYSA-N

InChI=1S/C18H20O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,19-20H,3-4H2,1-2H3/b18-17+

4-[(E)-4-(4-hydroxyphenyl)hex-3-en-3-yl]phenol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.32 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 25.0 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 2: ≥ 2.5 mg/mL (9.32 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)