Giredestrant
Based on 6 publication(s) in Google Scholar
Giredestrant (GDC-9545) is an orally active, full, selective Estrogen receptor α (ERα) degrader and antagonist with a DC50 of 0.03 nM. Giredestrant promotes the degradation of ERα protein, including the ESR1Y537S mutant ERα. Giredestrant reduces uterine wet weight in immature rats and induces a low cuboidal phenotype in their endometrial epithelium. Giredestrant induces tumor regression in both ESR1Y537S mutant and wild-type ERα tumor models. Giredestrant can be used for the research of ER+ breast cancer.
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- Pureza: 98.98%
- No. CAS: 1953133-47-5
- Fòrmula: C27H31F5N4O
- Peso molecular:522.55
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Giredestrant
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
ERα 0.03 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MCF7 | EC50 |
0.4 nM
Compound: 35; GDC-9545
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Antiproliferative activity against human MCF-7 cells incubated for 72 hrs by Cell-titer Glo assay
Antiproliferative activity against human MCF-7 cells incubated for 72 hrs by Cell-titer Glo assay
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[PMID: 34251202] |
In Vitro
Giredestrant potently inhibits ERα-mediated luciferase activity in T-47D wild-type breast cancer cells, with an IC50 of 0.05 nM[1].
Giredestrant potently degrades ERα in MCF-7 wild-type breast cancer cells, with a DC50 of 0.03 nM and a maximum degradation efficiency of 101%[1].
Giredestrant inhibits the proliferation of MCF-7 wild-type breast cancer cells, with an EC50 of 0.4 nM[1].
Giredestrant (0.1 nM-1 μM; 24 h) induces significant ERα degradation in ER+ breast cancer cell lines including CAMA-1, EFM-19, HCC1500, MCF-7, MDA-MB-134VI, MDA-MB-330 and T-47D starting at a concentration of 0.1 nM, and exhibits higher efficiency than GDC-0810 (HY-12864) and GDC-0927 (HY-111484)[1].
Giredestrant (1 nM; 0.5-24 h) promotes rapid degradation of ERα in MCF-7 breast cancer cells, with a half-life of 1.8 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:CAMA-1, EFM-19, HCC1500, MCF-7, MDA-MB-134VI, MDA-MB-330, T-47D ER+ breast cancer cell lines
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Concentration:0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM
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Incubation Time:24 h
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Result:Promoted significant ERα degradation across all seven tested cell lines, starting at the lowest concentration of 0.1 nM.
Was a more efficient degrader than fulvestrant, GDC-0810, and GDC-0927 in all cell lines.
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Cell Line:MCF-7 wild-type breast cancer cells
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Concentration:1 nM
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Incubation Time:0.5, 1, 2, 4, 6, 24 h
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Result:Promoted rapid ERα turnover with a half-life of 1.8 h, which was faster than GDC-0927 (6.0 h) and GDC-0810 (16.5 h), and comparable to Fulvestrant (HY-13636) (2.2 h).
Induced the highest ERα degradation at 24 h among the tested compounds.
Parmacokinetics
| Species | Dose | Route | Bioavailability |
|---|---|---|---|
| Rat[1] | 1 mg/kg | p.o. | 41 % |
In Vivo
Giredestrant (0.1-1 mg/kg; p.o.; once daily; for 29 consecutive days) induces tumor regression in the ESR1Y537S-mutant ER+ breast cancer PDX model, even when administered at a daily oral dose as low as 0.1 mg/kg[1].
Giredestrant (3 mg/kg; p.o.; once daily; for 26 consecutive days) inhibits the growth of wild-type ER+ breast cancer xenografts by up to 79%; when combined with Palbociclib (HY-50767), it induces a maximum tumor regression of 108%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immature female rats[1]
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Dosage:0.1 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 4 days
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Result:Caused a statistically significant reduction in the ratio of uterine wet weight to body weight at 10 mg/kg, comparable to the positive control SERD 11.
Induced low cuboidal uterine epithelial cells at 10 mg/kg, consistent with inverse agonism.
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Animal Model:Immunocompromised mice (PDX model host)[1]
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Dosage:0.1 mg/kg; 1 mg/kg
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Administration:p.o.; daily; 29 days
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Result:Suppressed tumor growth at 0.1 mg/kg and 1 mg/kg.
Induced tumor regression at 1 mg/kg, comparable to the positive control SERD 11 at 100 mg/kg.
Achieved 1 mg/kg efficacy with 10-fold lower plasma concentration than SERD 11 at 100 mg/kg, while promoting 1.8-fold higher ERα turnover.
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Animal Model:Immunocompromised mice (xenograft model host)[1]
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Dosage:3 mg/kg (single agent); 3 mg/kg (in combination with palbociclib 50 mg/kg)
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Administration:p.o.; daily; 26 days
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Result:Inhibited tumor growth by 79% as a single agent at 3 mg/kg.
Induced tumor regression up to 108% after 24 days when combined with palbociclib at 3 mg/kg, outperforming the combination of fulvestrant and palbociclib.
Resulted in well-tolerated treatments across all groups.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1953133-47-5
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Appearance Solid
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Peso molecular 522.55
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Fòrmula C27H31F5N4O
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Color Off-white to yellow
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SMILES
OCC(F)(F)CN([C@@H]1C2=C(F)C=C(NC3CN(CCCF)C3)C=C2F)[C@H](C)CC4=C1NC5=C4C=CC=C5
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Synonyms
GDC-9545; RG6171
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (6)
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Journal Impact Factor
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Most Recent
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Cancer Discov
2024 Feb 8;14(2):274-289. PMID: 37982575 -
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bioRxiv
Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells. [Abstract]2024 Jun 2:2024.05.28.596307. PMID: 38854123 -
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Solvente y solubilidad
In Vitro:
DMSO : 50 mg/mL (95.68 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.78 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.78 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (284 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9137 mL | 9.5685 mL | 19.1369 mL | 47.8423 mL |
| 5 mM | 0.3827 mL | 1.9137 mL | 3.8274 mL | 9.5685 mL | |
| 10 mM | 0.1914 mL | 0.9568 mL | 1.9137 mL | 4.7842 mL | |
| 15 mM | 0.1276 mL | 0.6379 mL | 1.2758 mL | 3.1895 mL | |
| 20 mM | 0.0957 mL | 0.4784 mL | 0.9568 mL | 2.3921 mL | |
| 25 mM | 0.0765 mL | 0.3827 mL | 0.7655 mL | 1.9137 mL | |
| 30 mM | 0.0638 mL | 0.3189 mL | 0.6379 mL | 1.5947 mL | |
| 40 mM | 0.0478 mL | 0.2392 mL | 0.4784 mL | 1.1961 mL | |
| 50 mM | 0.0383 mL | 0.1914 mL | 0.3827 mL | 0.9568 mL | |
| 60 mM | 0.0319 mL | 0.1595 mL | 0.3189 mL | 0.7974 mL | |
| 80 mM | 0.0239 mL | 0.1196 mL | 0.2392 mL | 0.5980 mL |
Giredestrant Related Classifications
HY-109176 Related Classifications
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Keywords
- Giredestrant
- 1953133-47-5
- GDC-9545
- RG6171
- GDC9545
- GDC 9545
- RG6171
- RG 6171
- RG-6171
- Estrogen Receptor/ERR
- immature rats
- human liver microsomes
- T-47D wild-type breast cancer cells
- MCF-7 wild-type breast cancer cells
- ER+ breast cancer cells
- ERα
- ESR1 Y537S mutant ERα
- hERG channels
- estrogen receptor alpha
- rat liver microsomes
- Inhibitor
- inhibitor
- inhibit