4-Hydroxytamoxifen CAS 68047-06-3

1. Anti tumor research: the "gold standard" of breast cancer treatment
The most core and well-known use is its outstanding performance in the research and treatment of breast cancer.
1.1. Selective estrogen receptor antagonists
It is a potent selective estrogen receptor modulator (SERM). It can bind to estrogen receptors (ER) and estrogen related receptors (ERR), exhibiting both estrogenic and antiestrogenic effects. The inhibitory IC ₅ ₀ value of [³ H] estradiol binding to estrogen receptors is only 3.3 nM, and it can significantly inhibit the binding of [³ H] estradiol to human 8S estrogen receptors at concentrations of 10 nM and 100 nM.

In breast tissue, it acts as an estrogen antagonist, blocking the stimulating effect of estrogen on breast tissue, thereby slowing down or stopping the growth of existing cancer cells and preventing the formation of new tumors.

1.2. In vitro anti-tumor activity
Numerous in vitro studies have confirmed the inhibition of both normal and cancerous breast cell growth. Research has shown that it exhibits higher potency than its precursor tamoxifen - in vitro, its binding affinity to estrogen receptors is similar to estradiol, and its potency far exceeds that of tamoxifen.

1.3. In vivo anti-tumor effect
The substance released through the skin has been shown to have significant anti-tumor effects on human breast tumors growing subcutaneously in mice. In limited human experiments, transdermal drug delivery can be concentrated in local breast tumors with only minimal systemic distribution. This characteristic makes it an ideal candidate drug for local treatment of breast cancer.

1.4. Potential to replace tamoxifen
Because tamoxifen has obvious side effects such as endometrial cancer, deep vein thrombosis, pulmonary embolism, changes in liver enzyme levels, and eye toxicity (including cataract), as well as adverse reactions such as hot flashes, vaginal secretions, depression, amenorrhea, and nausea, many cancer researchers recommend using 4-hydroxytamoxifen as an alternative drug to treat breast cancer. Showing tissue specificity for tissues that are easily receptive to estrogen, as an estrogen antagonist in breast tissue, it is expected to overcome many of the shortcomings of tamoxifen.

2. Gene editing revolution: CRISPR/Cas9's' precise switch '
This is the most exciting emerging use of 4-hydroxytamoxifen in recent years, and can be regarded as a "game changer" in the field of molecular biology.
2.1. Activate conditional Cas9 protein
Can activate inactive Cas9 containing peptide connections, thereby reducing off target CRISPR mediated gene editing. The mechanism is that 4-OHT binds to the Cas9 protein fused with the estrogen receptor ligand binding domain (ERT2), inducing a conformational change in Cas9 and transforming it from an inactive state to an active state.

2.2. Significantly improve gene editing specificity
In human cells, the specificity of target genome sites modified by conditionally active Cas9 is 25 times higher than that of wild-type Cas9. This discovery was published in Nature Chemical Biology (IF: 12.154) and first reported by Davis KM et al. in 2015. This means that the addition of 4-hydroxytriphenylamine can enable the CRISPR/Cas9 system to work only when needed, greatly reducing off target effects and providing a new guarantee for the safety of gene therapy.

2.3. Spatiotemporal controllable gene editing
Due to the ability of 4-hydroxytriphenylamine to control the activity of Cas9 through addition or elution, researchers can achieve precise spatiotemporal regulation of gene editing - adding 4-OHT at specific time points to initiate editing, and stopping editing after elution. This "reversible switch" characteristic makes it an indispensable tool molecule in basic research and gene therapy.

3. Neuroprotection: the 'neural guardian' against drug damage
It has also demonstrated remarkable protective effects in the field of neuroscience.
3.1. Reduce methamphetamine induced dopamine neurotoxicity
Research has shown that (6 μ g/0.1 mL sesame oil/day, subcutaneous injection) can effectively reduce the consumption of dopamine in the substantia nigra striatum induced by methamphetamine (MA) in intact and excised C57BL/6J mice.

In animal experiments, after three consecutive days of injection, the dopamine content in the striatum of mice was maintained without significant decrease.
3.2. Protect dopaminergic neurons
It does not alter the basal dopamine levels in the striatum, indicating that its protective effect is targeted towards damaging stimuli rather than simply increasing dopamine levels. This characteristic makes it potentially valuable for research on neurodegenerative diseases such as Parkinson's disease.

4. Signal pathway research: multi-target 'molecular probes'
Due to its multi-target activity, it has become a universal tool in the study of cell signaling pathways.

4.1. The gold standard for estrogen receptor/ERR research
It is a classic tool molecule for studying the signaling pathways of estrogen receptor (ER) and estrogen related receptor (ERR). It binds to estrogen receptors and estrogen related receptors, exhibiting estrogenic and antiestrogenic effects. In signal pathway research, it is widely used for:
Evaluation of proliferation inhibition of ER positive breast cancer cells
Research on transcriptional regulation of estrogen dependent genes
Screening for novel SERM drugs

4.2. Protein kinase C (PKC) inhibitors
According to reports, purified protein kinase C (PKC) can be irreversibly inhibited in vitro by oxidative inactivation of the catalytic domain. PKC is a key regulatory factor for cell proliferation, differentiation, and apoptosis, and its inhibitory effect adds a new dimension to the anti-tumor mechanism of 4-hydroxytamoxifen.
4.3. Lipid peroxidation inhibitors
4-hydroxytriphenylamine has been shown to inhibit lipid peroxidation. This antioxidant property makes it potentially valuable in the study of oxidative stress-related diseases, including neurodegenerative diseases, cardiovascular diseases, etc.