Estradiol is an endogenous estrogen receptor ligand that binds the ligand-binding domain of ERα and ERβ and provides a foundational recognition scaffold for nuclear receptor chemical biology. In targeted degradation research, estradiol-derived motifs can be used to design estrogen receptor-directed degraders when linker attachment preserves receptor engagement and supports ternary complex formation. In a bifunctional degrader, the estradiol-derived warhead binds the receptor, while an attached E3 ligase recruiter promotes proximity to ubiquitination machinery. The intended mechanism is receptor ubiquitination and proteasome-dependent depletion, enabling comparison of hormone-mediated receptor activation with induced protein removal. Estradiol is useful for estrogen receptor degrader exploration, ligand-binding domain studies, nuclear receptor signaling research, transcriptional regulation analysis, linker-vector optimization, and evaluation of hormone-derived warheads in targeted protein degradation platforms.
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| Size | Price | Stock | Quantity |
|---|---|---|---|
| 25 g | $197 | In stock |
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Target: This ligand targets estrogen receptors ERα/ESR1 and ERβ/ESR2 in biochemical or cellular target-engagement studies.
Mechanism of Action: Used as the target-protein recognition element, this ligand provides the binding interface for estrogen receptors ERα/ESR1 and ERβ/ESR2. In PROTAC design, a derivatizable position on the ligand can be connected through an optimized linker to an E3 ligase ligand, such as a CRBN, VHL, or IAP recruiter, while preserving productive target engagement. The resulting bifunctional molecule brings estrogen receptors ERα/ESR1 into proximity with the recruited E3 ligase, enabling ternary-complex formation. If the complex has favorable geometry and residence time, target lysine ubiquitination is promoted, leading to proteasome-dependent degradation in experimental systems.
Applications• ER Targeting PROTAC Development: Estradiol can serve as an ER-binding ligand to construct PROTACs that recruit an E3 ubiquitin ligase and drive selective ubiquitination. This enables systematic evaluation of ER degradation efficiency, dose–response behavior, and degradation kinetics in ER-positive cellular models, supporting mechanism-focused optimization of linker length and PROTAC architecture.
• Mechanism Studies of ER Degradation: Using estradiol-derived binding motifs in PROTACs allows dissection of how ER ubiquitination and proteasome-dependent turnover contribute to loss of receptor signaling. Researchers can compare degradation versus inhibition phenotypes, map pathway dependencies, and quantify downstream transcriptional changes to clarify whether degradation yields distinct biological outcomes.
• Optimization of Binding–Degradation Tradeoffs: Estradiol-based ligands provide a controllable handle for tuning affinity and residence time within PROTACs. By varying linker composition and attachment sites, investigators can assess how changes in ER engagement translate into altered ternary complex formation, ubiquitin transfer efficiency, and overall degradation potency.
• Profiling Cellular Selectivity and Resistance: Estradiol-targeted PROTACs can be used to evaluate context-dependent selectivity across ER expression levels and cofactor states. Experimental designs may include monitoring degradation in the presence of pathway modulators, comparing ER isoforms, and identifying resistance mechanisms such as altered E3 ligase availability or changes in proteostasis capacity.
| ConcentrationVolumeMass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 3.6713 mL | 18.3567 mL | 36.7134 mL |
| 5 mM | 0.7343 mL | 3.6713 mL | 7.3427 mL |
| 10 mM | 0.3671 mL | 1.8357 mL | 3.6713 mL |
| 50 mM | 0.0734 mL | 0.3671 mL | 0.7343 mL |
Estradiol is a BET bromodomain target ligand intended for use as the target-engaging component or reference ligand in PROTAC discovery workflows. Its known small-molecule recognition profile enables rational linker-vector evaluation and comparative degrader design. This molecule is described in detail below.
Structure: The structure of Estradiol is characterized by phenol or alcohol functionality; steroid or fused polycyclic hydrophobic core. These features provide defined hydrogen-bonding, hydrophobic, and steric elements that can support affinity retention while enabling analogue-based linker-vector selection.
Reactivity: The hydroxy or phenolic motif can be considered for ether, carbonate, carbamate, or ester linker attachment after SAR verification. For PROTAC construction, the POI ligand can be paired with CRBN ligands such as thalidomide, pomalidomide, or lenalidomide analogues, VHL ligands such as VH032 derivatives, or less common IAP/MDM2/cIAP-recruiting ligands, with alkyl, PEG, piperazine, triazole, or amide linkers screened for ternary-complex formation. In practice, incorporation into PROTACs should begin from derivatives that preserve the reported binding pharmacophore, followed by systematic variation of linker length, polarity, rigidity, and exit-vector geometry to optimize target engagement, E3 recruitment, and cellular degradation readouts.
How does estradiol affect the state of estrus in rats ?
Good morning! Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat.
7/7/2019
Dear Sirs, what is the activity of Estradiol in primary bone cell cultures ?
Yes. Estradiol inhibits both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria.
20/5/2021
Does it also called 17β-estradiol?
Yes, it is.
25/6/2021
Hi, what is the pKa of it?
Estradiol is a weak base, and its pKa is 10.2.
15/1/2022
Can you tell me in what form estradiol is excreted in animals ?
OK! Estradiol is excreted in the form of glucuronide and sulfate estrogen conjugates in urine.
28/3/2022
increase spine density
Working out great! In our mice models, Estradiol reversed the ovariectomy-induced decrease in spine density. Recommend everyone to use.
30/6/2018
induce neural differentiation
Used in our lab, no complaints, worked well. Estradiol induces new dendritic spines and synapses on hippocampal CA1 pyramidal cells and induces neural differentiation increased neurite branching of human endometrial stem cells.
31/1/2021
rescue the molecular and functional deficits
We injected Estradiol subcutaneously into the FBN-ARO-KO mice and found that it rescued the molecular and functional defects of the FBN-ARO-KO mice. Far beyond our expectations!
3/8/2021
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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