Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to reduce the risk of breast cancer in those at high risk. It is taken by mouth. Common side effects include hot flashes,

leg cramp A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the a ...

s, swelling, and joint pain. Severe side effects may include

blood clots A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. Use during pregnancy may harm the baby. The medication may worsen menstrual symptoms. Raloxifene is a

selective estrogen receptor modulator Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...

(SERM) and therefore a mixed

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

–

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of the estrogen receptor (ER). It has estrogenic effects in bone and antiestrogenic effects in the breasts and uterus. Raloxifene was approved for medical use in the United States in 1997. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2020, it was the 292nd most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses

Raloxifene is used for the treatment and prevention of

in postmenopausal women. It is used at a dosage of 60 mg/day for both the prevention and treatment of osteoporosis. In the case of either osteoporosis prevention or treatment, supplemental calcium and vitamin D should be added to the diet if daily intake is inadequate. Raloxifene is used to reduce the risk of breast cancer in postmenopausal women. It is used at a dosage of 60 mg/day for this indication. In the Multiple Outcomes of Raloxifene (MORE) clinical trial, raloxifene decreased the risk of all types of breast cancer by 62%, of invasive breast cancer by 72%, and of invasive estrogen receptor-positive breast cancer by 84%. Conversely, it does not reduce the risk of estrogen receptor-negative breast cancer. There were no obvious differences in effectiveness of raloxifene in the MORE trial for prevention of breast cancer at a dosage of 60 mg/m²/day relative to 120 mg/m²/day. In the Study of Tamoxifen and Raloxifene (STAR) trial, 60 mg/day raloxifene was 78% as effective as 20 mg/day tamoxifen in preventing non-invasive breast cancer. Women with undetectable levels of estradiol (<2.7 pg/mL) have a naturally low risk of breast cancer and, in contrast to women with detectable levels of estradiol, do not experience significant benefit from raloxifene in terms of reduction of breast cancer risk.

Contraindications

Raloxifene is contraindicated in

lactating Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...

women or women who are or who may become

pregnant Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

. It also may be of concern to women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and

retinal vein thrombosis Central retinal vein occlusion, also CRVO, is when the central retinal vein becomes occluded, usually through thrombosis. The central retinal vein is the venous equivalent of the central retinal artery and both may become occluded. Since the centra ...

Side effects

Common side effects of raloxifene include hot flashes (25–28% vs. 18–21% for placebo),

vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates a vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal ...

, and

s (generally mild; 5.5% vs. 1.9% for placebo).Raloxifene label
Last updated 09/2007] Raloxifene does ''not'' cause breast tenderness, endometrial hyperplasia,

menstrual bleeding The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

, or

endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...

. It does not appear to affect

cognition Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

or memory. Raloxifene is a teratogen; i.e., it can cause developmental abnormalities such as birth defects. Raloxifene may infrequently cause serious blood clots to form in the

legs A leg is a weight-bearing and locomotive anatomical structure, usually having a columnar shape. During locomotion, legs function as "extensible struts". The combination of movements at all joints can be modeled as a single, linear element ...

, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, and vision changes. Black box warnings were added to the label of raloxifene in 2007 warning of increased risk of death due to stroke for postmenopausal women with documented coronary heart disease or at increased risk for major coronary events, as well as increased risk for deep vein thrombosis and pulmonary embolism. The risk of venous thromboembolism with raloxifene is increased by several-fold in postmenopausal women ( = 3.1). Raloxifene has a lower risk of thromboembolism than tamoxifen. In the MORE trial, raloxifene caused a 40% decrease in risk of cardiovascular events in women who were at increased risk for

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

, although there was no decrease in cardiovascular events for the group as a whole. A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen and raloxifene used to treat breast cancer, significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects. A recent human case report in July 2016 suggests that raloxifene may in fact, at some point, also stimulate breast cancer growth leading to a reduction of advanced breast cancer disease upon the withdrawal of the drug. Unlike other SERMs, such as tamoxifen, raloxifene has no risk of

uterine hyperplasia Uterine hyperplasia, or enlarged uterus, is a symptom, medical symptom in which the volume and size of the uterus in a female is abnormally high. It can be a symptom of medical conditions such as adenomyosis, uterine fibroids, ovarian cysts, and e ...

( = 0.8). Raloxifene does not increase the incidence of

breast pain Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...

or tenderness in postmenopausal women.

Overdose

Raloxifene has been studied in clinical trials across a dosage range of 30 to 600 mg/day, and was well-tolerated at all dosages.

Pharmacology

Pharmacodynamics

Mechanism of action

Raloxifene is a

(SERM) and hence is a mixed

and

of the estrogen receptor (ER) in different tissues. It has estrogenic activity in some tissues, such as bone and the liver, and antiestrogenic activity in other tissues, such as the breasts and uterus. Its

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

(K_d) for the ERα is approximately 50 pM, which is similar to that of estradiol. Relative to estradiol, raloxifene has been reported to possess about 8 to 34% of the

for the ERα and 0.5 to 76% of the affinity for the ERβ. Raloxifene acts as a partial agonist of the ERα and as a pure antagonist of the ERβ. In contrast to the classical ERs, raloxifene is an agonist of the

G protein-coupled estrogen receptor G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the ''GPER'' gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible ...

(GPER) ( = 10–100 nM), a membrane estrogen receptor.

Clinical effects

Raloxifene has antiestrogenic effects in the mammary glands in preclinical studies. In accordance, raloxifene reduces

breast density Breast cancer screening is the medical screening of asymptomatic, apparently healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test ...

in postmenopausal women, a known risk factor for breast cancer. It does not stimulate the uterus in postmenopausal women, and results in no increase in risk of

endometrial The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

thickening, vaginal bleeding, endometrial hyperplasia, or

. At the same time, raloxifene has minimal antiestrogenic effect in the uterus in premenopausal women. This may possibly be due to inadequate tissue exposure of the uterus to raloxifene in these estrogen-rich individuals. In premenopausal women, raloxifene increases levels of

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...

(FSH) and estradiol. Conversely, in postmenopausal women, raloxifene has been found to reduce levels of the gonadotropins, luteinizing hormone (LH) and FSH, while not affecting levels of estradiol. Raloxifene also decreases prolactin levels in postmenopausal women. In men, raloxifene has been found to disinhibit the hypothalamic–pituitary–gonadal axis (HPG axis) and thereby increase total testosterone levels. Due to the simultaneous increase in sex hormone-binding globulin (SHBG) levels however, free testosterone levels often remain unchanged in men during therapy with raloxifene. Raloxifene has estrogenic effects on liver protein synthesis. It increases SHBG levels in both pre- and postmenopausal women as well as in men. The medication decreases levels of

total Total may refer to: Mathematics * Total, the summation of a set of numbers * Total order, a partial order without incomparable pairs * Total relation, which may also mean ** connected relation (a binary relation in which any two elements are comp ...

and low-density lipoprotein (LDL) cholesterol, C-reactive protein, apolipoprotein B, and homocysteine. Conversely, it has little effect on levels of triglycerides and high-density lipoprotein (HDL). Raloxifene has been shown to inhibit the oxidation of LDL cholesterol '' in vitro''. The medication has been found to decrease insulin-like growth factor 1 (IGF-1) levels in pre- and postmenopausal women as well as in men. It has also been found to increase insulin-like growth factor binding protein 3 (IGFBP-3) levels in pre- and postmenopausal women. Due to activation of estrogen receptors in the liver, raloxifene has

procoagulatory Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...

effects, such as decreasing levels of fibrinogen and influencing levels of other coagulation factors. For these reasons, raloxifene increases the risk of thrombosis. Raloxifene increases

bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...

in postmenopausal women but decreases it in premenopausal women. In the MORE trial, the risk of

vertebral fracture A spinal fracture, also called a vertebral fracture or a broken back, is a fracture affecting the vertebrae of the spinal column. Most types of spinal fracture confer a significant risk of spinal cord injury. After the immediate trauma, there is ...

s was decreased by 30%, and bone mineral density was increased in the

spine Spine or spinal may refer to: Science Biology * Vertebral column, also known as the backbone * Dendritic spine, a small membranous protrusion from a neuron's dendrite * Thorns, spines, and prickles, needle-like structures in plants * Spine (zoolog ...

(by 2.1% at 60 mg, 2.4% at 120 mg) and femoral neck (2.6% at 60 mg, 2.7% at 120 mg). It has been found to possess estrogenic effects in adipose tissue in postmenopausal women, promoting a shift from an

android fat distribution Android fat distribution describes the distribution of human adipose tissue mainly around the trunk and upper body, in areas such as the abdomen, chest, shoulder and nape of the neck. This pattern may lead to an "apple”-shaped body or central ob ...

to a gynoid fat distribution. The medication has been found to increase levels of

leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...

, an adipokine.

Pharmacokinetics

Absorption

The

absorption Absorption may refer to: Chemistry and biology * Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which ...

of raloxifene is approximately 60%. However, due to extensive first-pass metabolism, the absolute bioavailability of raloxifene is only 2.0%. Raloxifene is rapidly absorbed from the

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

s upon oral administration.

Peak plasma levels Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose. It is a standard measurement in pharm ...

of raloxifene occur 0.5 to 6 hours after an oral dose. In healthy postmenopausal women treated with 60 mg/day raloxifene, peak circulating raloxifene levels normalized by dose and body weight were (i.e., divided by (mg/kg)), 0.50 ng/mL (500 pg/mL) after a single dose and 1.36 ng/mL (1,360 pg/mL after multiple doses).

Distribution

Raloxifene is widely distributed throughout the body. There is extensive distribution of raloxifene into the liver,

serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

s, and kidneys. The volume of distribution of raloxifene with a single 30 to 150 mg oral dose is approximately 2348 L/kg, which corresponds to ~170,000 L for a 72 kg person. Both raloxifene and its glucuronide

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s show high plasma protein binding (>95%), including to both albumin and α₁ acid glycoprotein, but not to sex hormone-binding globulin. More specifically, raloxifene is 98.2 ± 0.4% bound to plasma proteins.

Metabolism

Raloxifene is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

in the liver and undergoes

enterohepatic recycling Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. ...

. It is metabolized exclusively by glucuronidation and is not metabolized by the

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

system. Less than 1% of radiolabeled material in plasma comprises unconjugated raloxifene. The metabolites of raloxifene include several glucuronides. The elimination half-life of raloxifene after a single dose is 27.7 hours (1.2 days), whereas its half-life at steady state at a dosage of 60 mg/day is 15.8 to 86.6 hours (0.7–3.6 days), with an average of 32.5 hours (1.4 days). The extended half-life of raloxifene is attributed to enterohepatic recirculation and its high plasma protein binding. Raloxifene and its glucuronide conjugates are interconverted by reversible metabolism and enterohepatic recycling, which prolongs the elimination half-life of raloxifene with oral administration. The medication is deconjugated into its active form in a variety of tissues, including liver, lungs, spleen, bone, uterus, and kidneys.

Elimination

Raloxifene is mainly

excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...

and is eliminated in

feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...

. Less than 0.2% of a dose is excreted unchanged in urine and less than 6% of a dose is excreted in urine as glucuronide conjugates.

Chemistry

Raloxifene hydrochloride has the empirical formula C₂₈H₂₇NO₄S•HCl, which corresponds to a molecular weight of 510.05 g/mol. Raloxifene hydrochloride is an off-white to pale-yellow solid that is slightly soluble in water. Raloxifene is a benzothiophene derivative and is structurally distinct from the triphenylethylene SERMs like tamoxifen, clomifene, and toremifene. It is the only benzothiophene SERM to have been marketed. A benzothiophene SERM that was not marketed is

arzoxifene Arzoxifene (; developmental code name LY-353381) is a selective estrogen receptor modulator (SERM) of the benzothiophene group which was never marketed. It is a potent estrogen antagonist in mammary and uterine tissue while acting as an estrogen ...

(LY-353381).

Bazedoxifene Bazedoxifene, used as bazedoxifene acetate, is a medication for bone problems and possibly (pending more study) for cancer. It is a third-generation selective estrogen receptor modulator (SERM). Since late 2013 it has had U.S. FDA approval for ba ...

(Duavee, Viviant) and

pipendoxifene Pipendoxifene (INN) (developmental code name ERA-923) is a nonsteroidal selective estrogen receptor modulator (SERM) that was under development by Ligand Pharmaceuticals and Wyeth-Ayerst Laboratories (now Wyeth) for the treatment of breast cancer ...

(ERA-923) are structurally related to raloxifene but are technically not benzothiophenes and instead are indoles.

History

Raloxifene was approved in the United States for the prevention of postmenopausal osteoporosis in 1997, the treatment of postmenopausal osteoporosis in 1999, and to prevent or reduce the risk of breast cancer in certain postmenopausal women in 2007. It received orphan designation in 2005.

Society and culture

Names

''Raloxifene'' is the generic name of the drug and its and , while ''raloxifène'' is its and ''raloxifene hydrochloride'' is its , , and . It has also been known by the name ''keoxifene''. Raloxifene is sold mainly under the brand name Evista and to a lesser extent the brand name Optruma. It is also sold under a variety of other brand names in various countries.

Availability

Raloxifene is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe,

Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...

, New Zealand, South Africa, Latin America,

Southern Southern may refer to: Businesses * China Southern Airlines, airline based in Guangzhou, China * Southern Airways, defunct US airline * Southern Air, air cargo transportation company based in Norwalk, Connecticut, US * Southern Airways Express, M ...

, Eastern, and Southeastern Asia, and elsewhere in the world such as in Israel and Egypt. Raloxifene is provided in the form of 60 mg oral

tablet Tablet may refer to: Medicine * Tablet (pharmacy), a mixture of pharmacological substances pressed into a small cake or bar, colloquially called a "pill" Computing * Tablet computer, a mobile computer that is primarily operated by touching the s ...

Controversy

An editorial in

Lancet Oncology ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...

criticized the way that research about the medication for breast cancer prevention was released.

Research

Clinical studies of raloxifene for metastatic breast cancer in women have been conducted but found little effectiveness at 60 mg/day in those previously treated with tamoxifen, though modest effectiveness has been observed at higher doses. In contrast to tamoxifen, raloxifene is not approved for the treatment of breast cancer. Raloxifene has been studied in men for a variety of uses, such as for treatment of schizophrenia,

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

, and

. It has been studied in combination with

castration Castration is any action, surgical, chemical, or otherwise, by which an individual loses use of the testicles: the male gonad. Surgical castration is bilateral orchiectomy (excision of both testicles), while chemical castration uses pharmaceut ...

and bicalutamide, a nonsteroidal antiandrogen, for the treatment of prostate cancer. Raloxifene has been studied as an adjunct in the treatment of schizophrenia in

postmenopausal women Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

. A 2017 meta-analysis concluded that it was safe and effective for this indication, although further studies with larger sample sizes are needed for confirmation. It may be effective in women with less severe symptoms. A tissue-selective estrogen-receptor complex (TSEC) of estradiol and raloxifene has been studied in postmenopausal women. Raloxifene (60 mg/day) was reported to be effective in the treatment of pubertal gynecomastia in adolescent boys in a small retrospective chart review. Other SERMs are also known to be effective in the treatment of gynecomastia. Raloxifene has been reported to augment the

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

effects of selective serotonin reuptake inhibitors (SSRIs). June 18th 2020, Exscalate4CoV, the private-public consortium supported by the EU’s Horizon 2020 programme for research and innovation, led by Dompé farmaceutici and currently representing 18 partners (including Fraunhofer Institute, CINECA, Chelonia Applied Science, Swiss Institute of Bioinformatics and others) has requested access to clinical trials for the use of Raloxifene in COVID-19 patients. Raloxifene, already proven effective against Mers and Sars in preclinical tests, has been indicated as effective against SARS-CoV-2 by the “in-silico” research conducted by the consortium which has shown efficacy in countering the replication of the virus in cells. The IP for its use against SARS-CoV-2 has already been protected on May 6 2020 in the name Dompé farmaceutici, Fraunhofer Institute and KU Leuven, to facilitate the largest possible access. Raloxifene would be used in mildly symptomatic COVID-19 patients to halt the spread of infection. This result emerged from the first virtual (in silico) screening conducted on the Consortium’s supercomputers of more than 400.000 molecules (safe-in-man drugs and natural products) made available by Dompé farmaceutici and the partner Fraunhofer (IME) to the Consortium. The molecules were prioritized if in clinical stage or already on the market. 7.000 molecules with certain promising characteristics were tested.

References

External links

* * {{Portal bar , Medicine Diarylketones Benzothiophenes Eli Lilly and Company brands GPER agonists Phenol ethers Phenols Piperidines Selective estrogen receptor modulators World Anti-Doping Agency prohibited substances Wikipedia medicine articles ready to translate Vinylogous carboxylic acids

Medical uses

Contraindications

Side effects

Overdose

Pharmacology

Pharmacodynamics

Mechanism of action

Clinical effects

Pharmacokinetics

Absorption

Distribution

Metabolism

Elimination

Chemistry

History

Society and culture

Names

Availability

Controversy

Research

References

Further reading

External links