| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Giredestrant targets the estrogen receptor (ERα), a nuclear receptor that mediates the effects of estrogens in target tissues. As a selective estrogen receptor degrader (SERD), Giredestrant binds to ERα with high affinity, inducing a conformational change that promotes receptor degradation and blocks estrogen-driven transcriptional activity. The compound is a full antagonist with an IC50 of 0.05 nM in T-47D wild-type cells. By degrading the receptor rather than simply blocking it, Giredestrant provides more complete suppression of ER signaling, which is critical for overcoming endocrine resistance in breast cancer.
|
|---|---|
| ln Vitro |
Giredestrant (GDC-9545) is a new ER antagonist with favorable preclinical and mechanistic DMPK characteristics. Giredestrant's high ER binding capacity, total suppression of ER signaling, and enhanced DMPK profile could all contribute to its great in vivo efficacy [1].
Giredestrant exhibits potent in vitro activity as an ER antagonist and degrader. It has an IC50 of 0.05 nM in T-47D wild-type cells, indicating exceptionally high potency. The compound potently competes with estradiol for binding to ER and induces a conformational change within the ER ligand binding domain. In cell-based assays, Giredestrant effectively inhibits estrogen-driven transcriptional activity and promotes ER degradation. Its activity is significantly more potent than first-generation SERDs, making it a promising next-generation therapeutic for ER-positive breast cancer. |
| ln Vivo |
Giredestrant has demonstrated in vivo activity in preclinical models of ER-positive breast cancer. As an orally available SERD, it can be administered conveniently in animal studies. The compound effectively degrades ER in tumors and inhibits estrogen-driven tumor growth. Its oral bioavailability and potent activity make it a strong candidate for clinical development. Giredestrant is currently being evaluated in clinical trials for the treatment of ER-positive breast cancer, with the goal of overcoming resistance to current endocrine therapies.
|
| Enzyme Assay |
In vitro receptor binding assays for Giredestrant involve measuring its affinity for the estrogen receptor (ER). Competitive binding assays using radiolabeled estradiol are commonly used. The compound is incubated with ER and the radioligand, and the displacement is measured to calculate the binding affinity. Transactivation assays using ER-responsive luciferase reporters are used to measure functional antagonism. ER degradation is assessed by Western blot or ELISA in cells treated with the compound. These assays confirm the compound’s mechanism as a potent SERD and full ER antagonist.
|
| Cell Assay |
In vitro cellular assays for Giredestrant are conducted in ER-positive breast cancer cell lines such as T-47D and MCF-7. Cells are treated with the compound at various concentrations, and ER transcriptional activity is measured using luciferase reporter assays. ER protein levels are measured by Western blot to assess degradation. Cell proliferation is measured using MTT or CellTiter-Glo assays to determine the compound’s anti-proliferative effects. These assays characterize the compound’s activity as a SERD and its potential for treating ER-positive breast cancer.
|
| Animal Protocol |
In vivo animal experiments with Giredestrant are conducted in mouse xenograft models of ER-positive breast cancer. Immunodeficient mice are engrafted with ER-positive breast cancer cells (e.g., MCF-7, T-47D). Giredestrant is administered orally at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of ER levels and signaling pathways. Pharmacodynamic studies are performed to confirm ER degradation and target engagement. These studies support the clinical development of Giredestrant for ER-positive breast cancer.
|
| ADME/Pharmacokinetics |
Giredestrant is an orally available compound with favorable pharmacokinetic properties. It has good oral bioavailability and is suitable for once-daily dosing. The compound’s half-life and tissue distribution have been characterized in preclinical studies. Its pharmacokinetic profile supports its use in clinical trials for ER-positive breast cancer. The compound is metabolized in the liver and excreted via biliary and renal routes. The fluorine atoms in its structure contribute to metabolic stability and potency.
|
| Toxicity/Toxicokinetics |
Giredestrant has been evaluated for safety in preclinical and clinical studies. The compound is generally well-tolerated at therapeutic doses. Common adverse effects may include those related to estrogen deprivation, such as hot flashes, fatigue, and arthralgia. The compound’s safety profile is being characterized in ongoing clinical trials. As with other SERDs, long-term safety monitoring is important. The compound is intended for therapeutic use in ER-positive breast cancer.
|
| References | |
| Additional Infomation |
Giredestrant is an orally administered selective estrogen receptor degrader/downregulator (SERD) with potential antitumor activity. After oral administration, grridatrine specifically targets and binds to the estrogen receptor (ER), inducing conformational changes and promoting ER degradation. This blocks ER-mediated signaling and inhibits the growth and survival of ER-expressing cancer cells.
Giredestrant (GDC-9545) is a next-generation selective estrogen receptor degrader (SERD) developed for the treatment of ER-positive breast cancer. It is a non-steroidal ER ligand that acts as a full antagonist with an IC50 of 0.05 nM in T-47D cells. Giredestrant potently competes with estradiol for binding and induces ER degradation. The compound is orally active and has been designed to overcome resistance to current endocrine therapies. It is also known as GDC-9545, RG-6171, and RG6171. Giredestrant represents a major advance in targeted therapy for ER-positive breast cancer and is being evaluated in clinical trials. |
| Molecular Formula |
C₂₇H₃₁F₅N₄O
|
|---|---|
| Molecular Weight |
522.55
|
| Exact Mass |
522.24
|
| Elemental Analysis |
C, 62.06; H, 5.98; F, 18.18; N, 10.72; O, 3.06
|
| CAS # |
1953133-47-5
|
| Related CAS # |
Giredestrant tartrate;2407529-33-1
|
| PubChem CID |
121410806
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.333±0.06 g/cm3(Predicted)
|
| Boiling Point |
618.8±55.0 °C(Predicted)
|
| LogP |
4.8
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
37
|
| Complexity |
746
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
FC(C([H])([H])O[H])(C([H])([H])N1[C@]([H])(C([H])([H])[H])C([H])([H])C2C3=C([H])C([H])=C([H])C([H])=C3N([H])C=2[C@@]1([H])C1C(=C([H])C(=C([H])C=1F)N([H])C1([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])F)C1([H])[H])F)F
|
| InChi Key |
GQCXHIKRWBIQMD-AKJBCIBTSA-N
|
| InChi Code |
InChI=1S/C27H31F5N4O/c1-16-9-20-19-5-2-3-6-23(19)34-25(20)26(36(16)14-27(31,32)15-37)24-21(29)10-17(11-22(24)30)33-18-12-35(13-18)8-4-7-28/h2-3,5-6,10-11,16,18,26,33-34,37H,4,7-9,12-15H2,1H3/t16-,26-/m1/s1
|
| Chemical Name |
3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol
|
| Synonyms |
GDC-9545 RG6171GDC9545 RG-6171GDC 9545 RG 6171Giredestrant
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~95.68 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9137 mL | 9.5685 mL | 19.1369 mL | |
| 5 mM | 0.3827 mL | 1.9137 mL | 3.8274 mL | |
| 10 mM | 0.1914 mL | 0.9568 mL | 1.9137 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
