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.
