Good morning, Ms.

The drug that I want to present about is

tamoxifen, which is a breast cancer drug. The first is the SAR of

tamoxifen. Tamoxifen has a central aryl ethylene core, which

consists of a double bond between the carbon atoms and the

two phenyl rings. This structure is essential for its estrogen

receptor binding activity.

Next, it is the stereochemistry. Tamoxifen has a Z-isomer

configuration, which the phenyl rings are arranged on the same

side of the double bond, and it is crucial for tamoxifen’s

biological activity. The third SAR is the phenyl rings, the rings

have contributed to the overall structure and hydrophobic

nature of tamoxifen and they are involved in the interactions

with the hydrophobic region of estrogen receptors.

Additionally, tamoxifen has the ethoxy side chain that is

attached to the nitrogen atom and contributes to the overall

lipophilicity of tamoxifen. It plays a crucial role in estrogen

receptor binding. Besides, the next SAR of tamoxifen is diphenyl

butene structure. The length and arrangement of the carbon

chain between the phenyl rings are crucial for the selectivity of
tamoxifen to the estrogen receptors.

Last but not least, tamoxifen will undergo metabolism in the

liver to form the active metabolites, which is 4-

hydroxytamoxifen. This hydroxylation process is done at specific

positions, particularly in the 4-hydroxylation, and thus

enhances the binding affinity of tamoxifen to the estrogen

receptors.

Next, these are the pharmacological action and mechanism

of action. First, tamoxifen inhibits the proliferative effect of

estrogen on cancer cells. Tamoxifen is an estrogen receptor

antagonist, and it competitively binds to the estrogen

receptors, particularly in the alpha estrogen receptors, in the

breast tissue. Next, tamoxifen prevents the recurrence of breast

cancer in individuals with estrogen receptor positive tumors.

The mechanism is that the drug blocks the estrogen receptors,

and thus reduce the risk of estrogen-dependent breast cancer

recurrence.

Furthermore, tamoxifen has antiestrogenic effects on

humans by binding to the estrogen receptors and undergoing

metabolism to form 4-hydroxytamoxifen and endoxifen to

influence the cellular responses. Tamoxifen also controls the

growth of hormone-sensitive breast cancer cells by interfering

the estrogen signaling. The last action of tamoxifen is the

stimulation of uterine endometrial proliferation. Tamoxifen has

agonistic effects on the uterus, and it may lead to an increased

risk of endometrial hyperplasia and uterine cancer.

These are the uses of tamoxifen, it has been classified into

FDA approved indication and NON-FDA approved indication.

FDA is Food and Drug Administration. So first, for FDA approved

indication, tamoxifen is used for the treatment of breast cancer

in both females and males. It is also used in adjuvant treatment

of breast cancer after the patients have completed their

primary treatment of breast cancer with surgery and radiation.

Then, it is also used in treatment of female patients that have

ductal carcinoma in situ after surgery and radiation to reduce

the risk of invasive breast cancer. Tamoxifen can induce

ovulation in the women who do not produce eggs but wish to

become pregnant. Besides, tamoxifen also treat McCune-

Albright syndrome, which is a condition that may cause bone

disease, early sexual development and dark colored spots on

the skin of the children.

In opposite, the non-FDA approved indications has included

treatment of progressive or recurrent desmoid tumors in

combination with sulindac, treatment of endometrioid

histology that are recurrent, metastatic, or at high-risk.

Tamoxifen also treats the primary or secondary gynecomastia

along with breast pain and treats oligospermia in combination

with testosterone. Last, tamoxifen is also used in prophylaxis of

coronary arteriosclerosis in men with a triple vessel.

Then, it is about the potential adverse effect, for common

adverse effect, there are menopausal symptoms, such as hot

flashes, night sweats, vaginal dryness, and reduced sex drive.

Apart from that, are weight gain, fluid retention which causes

oedema, nausea, and fatigue. For rare adverse effect, the first is

deep venous thrombosis, which the blood clots in the large

veins abnormally. Next is the pulmonary emboli, it is the

abnormal blood clots in the lungs. Then, osteoporosis may

occur, which is the bone loss, and this only occur in the

premenopausal women. The other adverse effects are causing

cancer of uterine or endometrial cancer, and the last is stroke.

These are my references. Thank you.