A report on Antiestrogen and Raloxifene

Fulvestrant, a steroidal antiestrogen and a drug used in the treatment of breast cancer.

Antiestrogens include selective estrogen receptor modulators (SERMs) like tamoxifen, clomifene, and raloxifene, the ER silent antagonist and selective estrogen receptor degrader (SERD) fulvestrant, aromatase inhibitors (AIs) like anastrozole, and antigonadotropins including androgens/anabolic steroids, progestogens, and GnRH analogues.

- Antiestrogen

It has estrogenic effects in bone and antiestrogenic effects in the breasts and uterus.

- Raloxifene

6 related topics with Alpha

Tamoxifen, a nonsteroidal triphenylethylene antiestrogen and a widely used drug in the treatment of breast cancer.

Selective estrogen receptor modulator

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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).

Figure 2: Nolvadex (tamoxifen) 20-milligram tablets (UK)

Figure 3: The domain structures of ERα and ERβ, including some of the known phosphorylation sites involved in ligand-independent regulation.

Figure 4: Structural basis for the mechanism of estrogen receptor agonist and antagonist action. The structures shown here are of the ligand binding domain (LBD) of the estrogen receptor (green cartoon diagram) complexed with either the agonist diethylstilbestrol (top, ) or antagonist 4-hydroxytamoxifen (bottom, ). The ligands are depicted as space filling spheres (white = carbon, red = oxygen). When an agonist is bound to a nuclear receptor, the C-terminal alpha helix of the LBD (H12; light blue) is positioned such that a coactivator protein (red) can bind to the surface of the LBD. Shown here is just a small part of the coactivator protein, the so-called NR box containing the LXXLL amino acid sequence motif. Antagonists occupy the same ligand binding cavity of the nuclear receptor. However antagonist ligands in addition have a sidechain extension which sterically displaces H12 to occupy roughly the same position in space as coactivators bind. Hence coactivator binding to the LBD is blocked.

Figure 5: 4-hydroxytamoxifen (red) overlaid with 17β-estradiol (black)

Figure 6: Trans-form of clomifene with the triphenylethylene structure in red.

Figure 8: Chemical structure of toremifene

Figure 9: Raloxifene has a benzothiophene group (red) and is connected with a flexible carbonyl hinge to a phenyl 4-piperidinoethoxy side chain (green).

Figure 10: Chemical structure of nafoxidine with the dihydronapthalene group in red.

Figure 11: Chemical structure of lasofoxifene shows cis-oriented phenyls.

Figure 12: Bazedoxifene includes an indole system (red) which is connected to an amine through a benzyloxyethyl chain (green).

Figure 13: Chemical structure of ospemifene. Ethoxy side chain ends with a hydroxy group (red) instead of a dimethylamino group as with first-generation SERMs.

Figure 14: The ABCD steroid ring system in 17β-estradiol.

Figure 15: "A ring" (A) and "D ring" (D) marked in raloxifene.

Raloxifene is used for prevention and treatment of postmenopausal osteoporosis and breast cancer prevention in high-risk postmenopausal women with osteoporosis.

Different tissues have different degrees of sensitivity to the activity of endogenous estrogens, so SERMs produce estrogenic or antiestrogenic effects depending on the specific tissue in question as well as the percentage of intrinsic activity (IA) of the SERM.

Tamoxifen

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Selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men.

Crystallographic structure of afimoxifene (carbon = white, oxygen = red, nitrogen = blue) complexed with ligand binding domain of estrogen receptor alpha (ERα) (cyan ribbon).

In 2006, the large STAR clinical study concluded that raloxifene is also effective in reducing the incidence of breast cancer.

Tamoxifen interacts with certain other antiestrogens.

A dimer of the ligand-binding region of ERβ (PDB rendering based on ).

Estrogen receptor

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Estrogen receptors (ERs) are a group of proteins found inside cells.

The domain structures of ERα and ERβ, including some of the known phosphorylation sites involved in ligand-independent regulation.

A dimer of the ligand-binding region of ERα (PDB rendering based on ).

Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, raloxifene)

Antiestrogens (e.g., fulvestrant, ICI-164384, ethamoxytriphetol)

Estrogen receptor alpha

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One of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen.

Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, raloxifene)

Antiestrogens (e.g., fulvestrant, ICI-164384, ethamoxytriphetol)

Clomifene

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Medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome.

It has been found to be useful in the treatment of some cases of gynecomastia but it is not as effective as tamoxifen or raloxifene for this indication.

Even though clomifene has some estrogenic effect, the antiestrogenic property is believed to be the primary source for stimulating ovulation.

Estrogen receptor beta

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One of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen.

Selective estrogen receptor modulators (e.g., tamoxifen, raloxifene)

Antiestrogens (e.g., fulvestrant, ICI-164384)