BY13
Based on 1 Customer Validation
BY13 is a SRC-3 PROTAC degrader with a DC50 of 0.031 μM. BY13 selectively blocks the ER signaling pathway over that of androgen receptor (AR)) through down-regulating ERα level. BY13 potently overcomes endocrine resistance in breast cancer by inducing cell cycle arrest in G1 phase and apoptosis, with superior effect over Fulvestrant (HY-13636). BY13 significantly inhibits the growth of drug-resistant breast tumors without obvious toxicity in LCC2 xenograft mice model.
(Pink: SRC-3 ligand (HY-101447); Blue: Cereblon ligand (HY-41547); Black: linker (HY-176226)).
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- Pureté : 98.17%
- CAS No.: 3117131-00-4
- Formule: C35H35N9O4
- Masse moléculaire:645.71
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Stockage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
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ERα |
SRC-3 0.031 μM (DC50) |
In Vitro
BY13 (0.1-10 μM, 24 h) dose-dependently reduces SRC-3 and ERα protein level in MCF-7 cells with 71% and 85% degradation, respectively[1].
BY13 (0.01-10 μM, 36 h) potently inhibits proliferation of wild-type, mutant-type and drug-resistant breast cancer cells (IC50 of 0.003-0.35 μM for MCF-7, LCC2 and MCF-7D538G/Y537S/EGFR cells), and dose-dependently degrades SRC-3 and ERα in mutant-type cells (particularly in MCF-7Y537S cells at 0.1 μM)[1].
BY13 (0.1-10 μM, 3-48 h) effectively reduces SRC-3 and ERα protein level, superior to Fulvestrant (HY-13636), and reaches the maximal degradation after 36 h while almost no longer increase with time in LCC2 cells [1].
BY13 (0.01-20 μM, 36 h) dramatically decreases the protein level of SRC-3 (0.1 μM only) and ERα (1 μM only) (DC50 of 0.031 μM for SRC-3) with subtype selectivity favoring SRC-1 over SRC-2 in MCF-7 cells[1].
BY13 (0.01-5 μM, 24 h) down-regulates the protein level of AR while this effect is weaker compared to ERα in MCF-7 cells, and moderately inhibits AR-overexpressing LNCaP cells (IC50: 1.43 μM)[1].
BY13 (1 μM, 36 h) significantly reduces SRC-3 protein level depending on a ubiquitin proteasome system (UPS) pathway in MCF-7 cells (similar phenomena observed in LCC2 cells)[1].
BY13 (1 μM, 6 h, 40-76°C) can enter tumor cells and directly bind to SRC-3 with significantly enhancement of the SRC-3 protein thermal stability at high temperature in MCF-7 cells[1].
BY13 (10 μM, 6 h) induces the spatial proximity of SRC-3 and CRBN, followed by promoting the formation of the SRC-3-BY13-CRBN ternary complex in MCF-7 cells[1].
BY13 (0.01-10 μM, 36 h) significantly increases the mRNA expression of SRC-3 with the increasing concentrations and effectively reduces the mRNA level of ERα in LCC2 cells[1].
BY13 (1-20 μM, 48 h) significantly induces breast cancer cells apoptosis with enhancement of both early and late apoptosis in MCF-7 and LCC2 cells.
BY13 (5-20 μM, 48 h) dose-dependently arrests LCC2 cells in the G1 phase, and thecell proportion is significantly higher than that in the S phase.
BY13 (0.01-100 μM) has sufficient metabolic stability and an acceptable safety profile with IC50 of 2.73 and 1.1 μM for CYP3A4 and hERG channel.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 cells, LCC2 cells
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Concentration:0.01, 0.1, 1, 5, 10 μM
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Incubation Time:24 h
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Result:Degraded both SRC-3 and ERα protein in MCF-7 cells at 1 μM with 71% and 85% degradation, respectively.
Dose-dependently reduced SRC-3 and ERα protein level in MCF-7 cells without a canonical “hook effect” as well as significantly degrades SRC-3 and ERα in LCC2 cells, superior to Fulvestrant (HY-13636).
Down-regulated the protein level of AR while this effect is weaker compared to ERα in MCF-7 cells
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Cell Line:MCF-7 cells, LCC2 cells
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Concentration:1 μM
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Incubation Time:MCF-7 cells (3, 6, 9, 12, 24, 36 h), LCC2 cells (3, 6, 9, 12, 24, 36, 48 h)
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Result:Effectively reduced the SRC-3 protein level after 24h and reached the maximal degradation in MCF-7 cells at 36 h. Significantly reduced the protein level of SRC-3 after only 9 h of treatment, and reached the maximal degradation in LCC2 cells at 36 h with almost no longer increase of degradation.
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Cell Line:MCF-7 cells, LCC2 cells
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Concentration:1 μM after 1 μM of MG-132, Bortezomib, Chloroquine or (BY13-Neg, SI-2 and Pomalidomide) for 2 h
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Incubation Time:36 h
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Result:Significantly reduced SRC-3 protein level depending on a ubiquitin proteasome system (UPS) pathway, but this effect was reversed by two proteasome inhibitors (MG-132, Bortezomib and SI-2) not by BY13-Neg in MCF-7 cells (similar symptoms observed in LCC2 cells).
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Cell Line:MCF-7 cells, LCC2 cells
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Concentration:1, 5, 10, 20 μM
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Incubation Time:48 h
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Result:Effectively induced cell apoptosis with enhancement of both early and late apoptosis in MCF-7 cells at increased concentrations (35% maximal early apoptosis rate).
Mainly induced the late apoptosis at 1 μM, but resulted in early apoptosis at 10 μM and induced a strong early apoptotic effect at 20 μM (＞ 30% early apoptosis rate) in LCC2 cells.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | AUC0-t | AUC0-∞ | Tmax |
|---|---|---|---|---|---|---|---|
| Mice | 2 mg/kg | i.v. | 3.44 h | 147.85 ng/mL | 318.39 ng·h/mL | 367.1 ng·h/mL | / |
| Mice | 20 mg/kg | p.o. | 4.49 h | 25.44 ng/mL | 47.07 ng·h/mL | 58.39 ng·h/mL | 0.33 h |
| Mice | 4 mg/kg | i.p. | 3.46 h | 31.19 ng/mL | 49.14 ng·h/mL | 55.19 ng·h/mL | 0.33 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female Balb/c nude mice (4 weeks old) were injected subcutaneously into the right lower axilla with LCC2 cells (5 × 106 cells/mouse) to induce LCC2 xenograft mice model[1].
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Dosage:3, 5 10 μM/kg, Tamoxifen (10 μM/kg) and Fulvestrant (5 μM/kg)
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Administration:i.p., once every two days for 23 days after tumors reached approximately 100 mm3, and then collected sample at 36 day1.
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Result:Significantly inhibited tumor growth at 3 μM/kg, with superior effect of 54% tumor growth inhibition rate 54% at 5 μM/kg.
Almost completely degraded SRC-3 protein within the tumor tissues at 3 μM/kg, and the protein levels of both SRC-3 and ERα were further decreased at 5 μM/kg.
Had a wide therapeutic window, without effect weight gain of mice model up to 10 μM/kg.
Had a high safety property without observable histopathological changes in the organ tissues of mice model during the administration period at 3 and 5 μM/kg.
Improved the poor prognosis of endocrine-resistant breast cancer with reducement of ki67 level in tumor tissues at 3 and 5 μM/kg.
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Protocol for Cell Cycle
- Breast Cancer Modeling
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Research Protocol for Endocrine Diseases
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS No. 3117131-00-4
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Appearance Solid
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Masse moléculaire 645.71
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Formule C35H35N9O4
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Color Light yellow to brown
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SMILES
C/C(C1=NC=CC=C1)=N\NC2=NC(C=CC=C3)=C3N2C4CN(C4)C5CCN(CC5)C6=CC=CC7=C6C(N(C7=O)C8C(NC(CC8)=O)=O)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvant et solubilité
In Vitro:
DMSO : 50 mg/mL (77.43 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 (sealed storage, away from moisture). 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 (sealed storage, away from moisture). 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)
Pureté et documentation
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Fiche technique (301 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
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 (sealed storage, away from moisture). 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 | 1.5487 mL | 7.7434 mL | 15.4868 mL | 38.7171 mL |
| 5 mM | 0.3097 mL | 1.5487 mL | 3.0974 mL | 7.7434 mL | |
| 10 mM | 0.1549 mL | 0.7743 mL | 1.5487 mL | 3.8717 mL | |
| 15 mM | 0.1032 mL | 0.5162 mL | 1.0325 mL | 2.5811 mL | |
| 20 mM | 0.0774 mL | 0.3872 mL | 0.7743 mL | 1.9359 mL | |
| 25 mM | 0.0619 mL | 0.3097 mL | 0.6195 mL | 1.5487 mL | |
| 30 mM | 0.0516 mL | 0.2581 mL | 0.5162 mL | 1.2906 mL | |
| 40 mM | 0.0387 mL | 0.1936 mL | 0.3872 mL | 0.9679 mL | |
| 50 mM | 0.0310 mL | 0.1549 mL | 0.3097 mL | 0.7743 mL | |
| 60 mM | 0.0258 mL | 0.1291 mL | 0.2581 mL | 0.6453 mL |
BY13 Related Classifications
HY-176225 Related Classifications
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