| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
ER[1]
GNE-502 is a potent and selective ER degrader (SERD). It targets the Estrogen Receptor (ER) for proteasomal degradation. By binding to ER, it induces a conformational change that targets the receptor for destruction, effectively reducing ER protein levels and blocking downstream signaling. |
|---|---|
| ln Vitro |
GNE-502 is a potent inhibitor of the ER-ligand binding domain (LBD). It exhibits anti-proliferative effects in ER+ breast cancer cell lines. As a degrader, it effectively reduces cellular ERalpha protein levels, leading to a sustained inhibition of ER-dependent gene transcription and cell growth.
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| ln Vivo |
GNE-502 (10 and 100 mg/kg; po) has been investigated in a WT MCF7 tumor xenograft model due to its sufficient oral exposure[1]. Tumor growth inhibition dose-dependently is demonstrated by GNE-502 at 10 mg/kg and 30 mg/kg, with tumor stasis at 100 mg/kg[1].
In a WT MCF7 tumor xenograft model, GNE-502 demonstrates dose-dependent tumor growth inhibition at 10 mg/kg and 30 mg/kg, with tumor stasis observed at 100 mg/kg. It possesses sufficient oral exposure to be tested in vivo and shows robust efficacy in xenograft models, making it a valuable tool for studying ER+ cancer. |
| Enzyme Assay |
Cell-free ER binding assays are performed using a time-resolved fluorescence resonance energy transfer (TR-FRET) format. A GST-tagged ER ligand-binding domain (LBD), a terbium-labeled anti-GST antibody, and a fluorescein-labeled coactivator peptide are used. The compound's ability to competitively displace an agonist is measured, and the IC50 is determined by the loss of TR-FRET signal.
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| Cell Assay |
ER+ breast cancer cell lines (e.g., MCF-7, T47D) are seeded in 96-well plates and treated with a dilution series of GNE-502 for 5-7 days. Cell viability is measured using the CellTiter-Glo luminescent cell viability assay to calculate the half-maximal inhibitory concentration (IC50) for growth inhibition. Additionally, ERalpha protein levels are assessed via Western blot to confirm target degradation.
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| Animal Protocol |
Animal/Disease Models: Mouse[1]
Doses: 10 and 100 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: po; single dosage Experimental Results: Possessed sufficient oral exposure to be tested in a WT MCF7 tumor xenograft model. The in vivo efficacy of GNE-502 is evaluated in a xenograft mouse model. Female athymic nude mice are inoculated subcutaneously with MCF-7 ER+ breast cancer cells. When tumors reach a predetermined size, mice are randomized into treatment groups and GNE-502 is administered via oral gavage (p.o.) at doses ranging from 3 to 100 mg/kg daily. Tumor volumes are measured bi-weekly with calipers. Endpoints include tumor growth inhibition (TGI) and analysis of ERalpha levels in excised tumors by Western blot. |
| ADME/Pharmacokinetics |
GNE-502 is characterized by its excellent oral bioavailability and favorable pharmacokinetic profile. It is designed to achieve high and sustained systemic exposure, allowing for continuous ER degradation in vivo. Its PK properties support a once-daily oral dosing regimen, which is essential for maintaining target coverage and driving tumor regression in preclinical models.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that GNE-502 is well-tolerated at therapeutic doses. The primary observed effects are on-target pharmacodynamic effects related to ER degradation. No significant off-target toxicities have been reported in preclinical models, supporting its potential for further development as a therapeutic agent.
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| References | |
| Additional Infomation |
GNE-502 is a research-grade SERD that has demonstrated strong preclinical efficacy. It serves as a valuable tool for exploring the therapeutic potential of ER degradation in ER+ breast cancer models and may represent a lead compound for the development of next-generation oral SERDs. It is intended for research use only and is not approved for human consumption.
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| Molecular Formula |
C25H30FN3O3S
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|---|---|
| Molecular Weight |
471.59
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| Exact Mass |
471.199
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| CAS # |
1953134-16-1
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| Related CAS # |
(1S,3R)-GNE-502;1953134-15-0
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| PubChem CID |
121410723
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| Appearance |
White to off-white solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
763
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| Defined Atom Stereocenter Count |
2
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| SMILES |
N1C2=C(C=CC=C2)C2C[C@@H](C)N(S(C)(=O)=O)[C@H](C3=CC=C(OCCN4CC(CF)C4)C=C3)C1=2
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| InChi Key |
ALLRPIPLWLLBGX-CRICUBBOSA-N
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| InChi Code |
InChI=1S/C25H30FN3O3S/c1-17-13-22-21-5-3-4-6-23(21)27-24(22)25(29(17)33(2,30)31)19-7-9-20(10-8-19)32-12-11-28-15-18(14-26)16-28/h3-10,17-18,25,27H,11-16H2,1-2H3/t17-,25-/m1/s1
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| Chemical Name |
(1R,3R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (212.05 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1205 mL | 10.6024 mL | 21.2049 mL | |
| 5 mM | 0.4241 mL | 2.1205 mL | 4.2410 mL | |
| 10 mM | 0.2120 mL | 1.0602 mL | 2.1205 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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