Estradiol

 CAS No.: 50-28-2  Cat No.: BP-300106  Purity: >98%  HNMR  MS  HPLC 4.5  

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.

Estradiol

Structure of 50-28-2

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Ligand for Target Protein
Molecular Formula
C18H24O2
Molecular Weight
272.38
Appearance
White crystalline powder

* For research and manufacturing use only. Not for human or clinical use.

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25 g $197 In stock

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Purity
>98%
Solubility
Water: 3.6 mg/L
Appearance
White crystalline powder
Application
human sex hormone
Storage
2-8°C
IUPACName
(8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
Synonyms
Beta-Estradiol; 17beta-Estradiol; Oestradiol; Dihydrofolliculin
Melting Point
178.5 °C
Density
1.2±0.1 g/cm3
InChI Key
VOXZDWNPVJITMN-ZBRFXRBCSA-N
InChI
InChI=1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1
SMILES
CC12CCC3C(C1CCC2O)CCC4=C3C=CC(=C4)O
Stability
Stable. Incompatible with strong oxidizing agents.
Mechanism

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.

1. Fluorescence resonance energy transfer based aptasensor for the sensitive and selective detection of 17β-estradiol using a quantum dot-bioconjugate as a nano-bioprobe
Feng Long,* Hanchang Shi and Hongchen Wang. RSC Adv.,2014, 4,2935–2941
Accordingly, the storage stability of the proposed QD nano-bioprobe was investigated. When the QD nano-bioprobe was stored in a refrigerator at 4 oC and measured at 3 day intervals, the decrease in the average maximum signal response in the absence of the analyte was<10% for the 17β-estradiol aptamer after 45 days of storage. Meanwhile, even when the average signal response for the 17β-estradiol specific aptamer slightly decreased, the QD nano-biosensor specific response was unaffected because all measurements were normalized with respect to the blank signal at the beginning of the daily analysis, and the signal shifts in the blank and sample measurements were generally the same. Thus, the developed QD-based aptasensor had sufficient stability. The stability and robustness of the QD nano-bioprobe was highly advantageous compared with other assays reported for 17β-estradiol, which also indicated the reliability of the proposed aptasensor for 17β-estradiol measurements.
2. From "hemoabzymes" to "hemozymes": towards new biocatalysts for selective oxidations
J.-P. Mahy,* J.-D. Marechal and R. Ricoux. Chem. Commun., 2015, 51, 2476—2494
The four metalloporphyrin–estradiol conjugates bound to the antibody 7A3 with a 2/1 stoichiometry, showing that, despite the bulky porphyrin, the estradiol anchor was still well accommodated by the antibody. The dissociation constants for the 4 metalloporphyrin–estradiol–7A3 complexes remained quite good, when compared to the affinity of the antibody for estradiol (KD ≈ 10-9M), with respective KD values of 4× 10-7M and 2 × 10-6M for the Fe- and Mn(TMPyP)–estradiol–7A3 complexes and 2 × 10-6 M and 9 × 10-6M for the Fe– and Mn(TpSPP)–estradiol–7A3 complexes. The nature of the porphyrin (cationic or anionic), as well as that of the metal inserted had thus little influence on the association of the cofactor with the antibody.
3. A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation
Xiaoyan Liu, Yanqiu Liu, Mengchun Cheng, Xiaozhe Zhanga and Hongbin Xiao*. Mol. BioSyst., 2015, 11,635—646
However, metabolomics studies on osteoporosis models mainly focus on the effect of estrogen deficiency on the metabolome, and the effects of estradiol intervention is little researched. In addition, current biofluid (blood, urine etc.)metabolomics studies could merely provide downstream consequences caused by estradiol exposure, while lack of site and cell-specific effects evaluation. Evaluation of site- and cell-specific effects is particularly important for understanding the interaction mechanism between stimulus and targets. Using well-designed in vitro assays would provide complementary evidence for the in vivo studies, and give an insight into the specific interaction mechanism between estradiol and osteoporosis-related cells.
4. Interfacial nano-biosensing in microfluidic droplets for high-sensitivity detection of low-solubility molecules
Maowei Dou, JoseMireles Garcıa Jr., Sihui Zhan* and XiuJun Li*. Chem. Commun., 2016, 52, 3470—3473
Recently, aptamer-based electrochemical biosensors and aptamer-based optical biosensors have been developed for simple estradiol detection. However, because 17b-estradiol is almost insoluble in water, watermiscible organic solvents are required in these methods to dissolve estradiol, and the distribution ratio of each component needs to be carefully optimized to ensure that estradiol is completely dissolved. Thus, these assays usually require multi-step complicated procedures. These limitations compromise the advantages of detection simplicity fromaptamers, and hinder the extensive application of such detection approaches.
ConcentrationVolumeMass1 mg5 mg10 mg
1 mM3.6713 mL18.3567 mL36.7134 mL
5 mM0.7343 mL3.6713 mL7.3427 mL
10 mM0.3671 mL1.8357 mL3.6713 mL
50 mM0.0734 mL0.3671 mL0.7343 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

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