| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
(R)-GDC-0927 targets estrogen receptor alpha (ERalpha). It binds to ERalpha and promotes its proteasomal degradation, acting as a selective estrogen receptor degrader (SERD). The compound achieves ERalpha degradation with an IC50 of approximately 0.1-0.2 nM and a maximal degradation (Emax) of 97%. The (R)-enantiomer binds ERalpha through a co-crystal-validated 'core-flipped' binding mode involving the fluoromethyl azetidine side chain, which is structurally distinct from selective estrogen receptor modulators (SERMs). This binding directly promotes receptor degradation rather than simple antagonism.
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| ln Vitro |
(R)-GDC-0927 demonstrates potent ERalpha degradation in vitro. In comparative studies, the racemic compound achieved 97% reduction in ERalpha protein levels in tamoxifen-resistant breast cancer cell lines, outperforming earlier lead compounds (91% degradation). The compound inhibits estrogen-driven transcriptional activity and reduces MCF-7 breast cancer cell viability. Its non-steroidal nature and unique binding mode provide advantages over fulvestrant, the only approved SERD requiring intramuscular injection. The (R)-enantiomer is the active isomer responsible for the degradation activity.
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| ln Vivo |
In vivo, (R)-GDC-0927 demonstrates dose-dependent antitumor activity in ESR1 mutant and wild-type patient-derived xenograft (PDX) models of ER+ breast cancer. The efficacious dose range is 10-100 mg/kg/day, and the compound is well tolerated at these doses. It induces tumor regression in tamoxifen-resistant xenograft models where antagonists fail, showing superior efficacy compared to standard endocrine therapies. Oral administration once daily provides convenient dosing for longitudinal target engagement studies and maintained ERalpha degradation throughout the treatment period.
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| Enzyme Assay |
Cell-free ERalpha binding can be assessed using fluorescence polarization or time-resolved fluorescence resonance energy transfer (TR-FRET) assays with purified ERalpha ligand-binding domain. (R)-GDC-0927 is incubated with ERalpha protein and fluorescently labeled estradiol tracer. Competitive binding is measured by fluorescence polarization changes. However, as a SERD that induces degradation, the key activity is measured in cell-based assays rather than cell-free systems due to the requirement for the cellular degradation machinery.
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| Cell Assay |
ERalpha degradation assay protocol: ER+ breast cancer cells (e.g., MCF-7 or tamoxifen-resistant derivatives) are seeded in 6-well plates and treated with (R)-GDC-0927 at concentrations ranging from 0.01-1000 nM for 6-24 hours. Cells are lysed in RIPA buffer with protease inhibitors, and ERalpha protein levels are quantified by Western blot with normalization to beta-actin or GAPDH. IC50 values for degradation are calculated from densitometry analysis of dose-response curves. Cell viability is assessed by MTT or CellTiter-Glo assays after 72-96 hours of treatment.
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| Animal Protocol |
Xenograft protocol: Female athymic nude mice bearing established ER+ breast cancer xenografts (e.g., MCF-7 or patient-derived xenografts, approximately 150-300 mm3) are randomized (n=8-10/group) and treated with (R)-GDC-0927 orally at 10-100 mg/kg/day (once daily) or vehicle control. Tamoxifen or fulvestrant may be used as comparators. Tumor volumes are measured twice weekly by calipers, and body weights are recorded. At study endpoint, tumors are harvested for ERalpha Western blot analysis and Ki67 immunohistochemistry to assess proliferation.
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| ADME/Pharmacokinetics |
(R)-GDC-0927 is orally bioavailable with favorable pharmacokinetic properties suitable for once-daily dosing. In preclinical models, the compound achieves sufficient systemic exposure at 10-100 mg/kg/day to maintain ERalpha degradation throughout the dosing interval. Phase I clinical studies confirmed oral bioavailability in postmenopausal women. The compound likely undergoes hepatic metabolism, though specific metabolic pathways are not fully published. Its non-steroidal structure avoids the poor solubility and injection requirements associated with fulvestrant.
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| Toxicity/Toxicokinetics |
In preclinical toxicology, (R)-GDC-0927 was well tolerated at efficacious doses up to 100 mg/kg/day in xenograft studies, with no significant body weight loss or overt toxicity reported. In a Phase I open-label study of 42 postmenopausal women with ER+ metastatic breast cancer, there were no reports of dose-limiting toxicities (DLTs), treatment-related serious adverse events (SAEs), deaths, or adverse events leading to withdrawal. The safety profile supports continued clinical development for ER+ breast cancer.
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| References |
[1]. Wang L, er al. The Quest for Orally Available Selective Estrogen Receptor Degraders (SERDs). ChemMedChem. 2020 Nov 18;15(22):2072-2097.
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| Additional Infomation |
(R)-GDC-0927 (also known as SRN-927 and RG6047) completed a Phase I clinical trial in postmenopausal women with locally advanced or metastatic ER+ breast cancer. The study demonstrated dose-dependent antitumor activity and an acceptable safety profile with no DLTs or treatment-related SAEs. However, clinical development has been deprioritized or discontinued for undisclosed reasons, possibly related to strategic portfolio decisions or emerging competitive SERD candidates. The compound remains available for preclinical research as a reference standard and a tool for studying SERD pharmacology in ER+ breast cancer models. Not approved for clinical use.
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| Molecular Formula |
C28H28FNO4
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|---|---|
| Exact Mass |
461.2
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| CAS # |
1642297-53-7
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| Related CAS # |
GDC-0927;1642297-01-5;GDC-0927 Racemate;1443983-36-5
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| PubChem CID |
87054925
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
703
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C([C@H](OC2=C1C=C(C=C2)O)C3=CC=C(C=C3)OCCN4CC(C4)CF)C5=CC(=CC=C5)O
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| InChi Key |
KJAAPZIFCQQQKX-MUUNZHRXSA-N
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| InChi Code |
InChI=1S/C28H28FNO4/c1-18-25-14-23(32)7-10-26(25)34-28(27(18)21-3-2-4-22(31)13-21)20-5-8-24(9-6-20)33-12-11-30-16-19(15-29)17-30/h2-10,13-14,19,28,31-32H,11-12,15-17H2,1H3/t28-/m1/s1
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| Chemical Name |
(2R)-2-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-(3-hydroxyphenyl)-4-methyl-2H-chromen-6-ol
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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 |
| 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: 50 mg/mL (108.34 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.) |
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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