AZ'6421
Based on 1 Customer Validation
AZ'6421 is an orally active ERα PROTAC degrader with a DC50 of 0.4 nM. AZ'6421 recruits the VHL E3 ligase to form a ternary complex, inducing proteasome-mediated polyubiquitination and degradation of ERα. AZ'6421 inhibits the growth of ER+ cancer cells. AZ'6421 can be used in studies related to ER+ breast cancer.
(Pink: ERα ligand (HY-12870); Blue: VHL ligand (HY-125845); Black: linker (HY-176364)).
For research use only. We do not sell to patients.
- Purity: 98.13%
- CAS No.: 2361115-35-5
- Formula: C52H65F3N6O7S
- Molecular Weight:975.17
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
|
ERα 0.4 nM (DC50) |
VHL |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MCF7 | IC50 |
0.3 nM
Compound: Ex 38; Ex 72
|
Induction of VHL E3 ligase mediated ERalpha degradation in human MCF7 cells assessed as downregulation of ERalpha expression by cell-based immunofluorescence assay
Induction of VHL E3 ligase mediated ERalpha degradation in human MCF7 cells assessed as downregulation of ERalpha expression by cell-based immunofluorescence assay
|
[PMID: 31620216] |
AZ'6421 potently binds to the recombinant ERα ligand-binding domain, with an IC50 of <0.6 nM[1].
AZ’6421 (1 µM; 30 min) exhibits low intrinsic clearance of 22 µL/min/mg protein in mouse liver microsomes[1].
AZ’6421 (5 µM; 18 h) exhibits high protein binding in mouse plasma, with a free fraction of 0.02%[1].
AZ’6421 (0.3 pM-3 µM; 20-24 h) potently degrades ERα in MCF7 cells, with a DC50 of 0.4 nM, and achieves a maximum degradation rate of 100% relative to Fulvestrant (HY-13636)[1].
AZ'6421 (100-300 nM; 7 h)-mediated ERα degradation in MCF7 cells depends on proteasome activity[1].
Maximal degradation of ERα in MCF7 cells mediated by AZ’6421 (100-300 nM; 7 h) requires recruitment of the VHL E3 ligase[1].
AZ’6421 (6 days) potently inhibits the growth of MCF7 and CAMA1 cells, with IC50 values of 0.5 nM and 0.2 nM, respectively[1].
AZ'6421 (Example 72) exhibits anti-tumour activity via the ability to degrade the estrogen receptor in a number of different breast cancer cell-lines (MCF-7, CAMA-I, and BT474)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MCF7 cells
-
Concentration:100 nM, 300 nM (following 1 h pre-treatment with 10 µM MG132)
-
Incubation Time:7 h
-
Result:Induced ERα degradation that was attenuated by pre-treatment with MG132, confirming degradation occurs via the proteasome pathway.
-
Cell Line:MCF7 cells
-
Concentration:100 nM, 300 nM (following 1 h pre-treatment with 10 µM acetylated-(S,R,S)-AHPC)
-
Incubation Time:7 h
-
Result:Induced ERα degradation that was partially reduced by pre-treatment with excess VHL ligand, confirming maximal degradation requires VHL recruitment.
AZ'6421 (30-100 mg/kg; BID; 4 days) exhibits estrogenic agonist activity in immature female rats, as evidenced by increased uterine weight and tall columnar uterine epithelium, likely driven by its circulating partial agonist metabolite[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NOD scid gamma (NSG) (female)[1]
-
Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg (QD); 100 mg/kg (BID)
-
Administration:p.o.; QD/BID; 4 days (PD studies); ongoing schedule (efficacy studies)
-
Result:Induced a dose-dependent reduction in tumour ERα protein levels, with ~70% degradation achieved at 30 mg/kg QD.
Did not increase ERα degradation beyond ~70% when dose was increased to 100 mg/kg QD or BID.
Decreased tumour progesterone receptor (PGR) mRNA levels dose-dependently, with the 100 mg/kg BID dose achieving ~80% inhibition.
Resulted in 86% tumour growth inhibition at 100 mg/kg BID.
Showed no significant effect on tumour growth at 30 mg/kg QD.
-
Animal Model:Immature female rats[1]
-
Dosage:30 mg/kg; 100 mg/kg
-
Administration:BID; 4 days
-
Result:Showed a trend of increased uterine weight relative to vehicle control at both 30 mg/kg BID and 100 mg/kg BID.
Induced tall columnar uterine epithelium with increased cell size in treated rats, consistent with an estrogenic agonist effect.
Had substantial levels of circulating metabolite 8, which acts as a partial ER agonist in vitro.
Chemical Information
-
CAS No. 2361115-35-5
-
Appearance Solid
-
Molecular Weight 975.17
-
Formula C52H65F3N6O7S
-
Color White to off-white
-
SMILES
C[C@@H](N1CC(C)(F)C)CC2=C(NC3=C2C=CC=C3)[C@H]1C4=C(F)C=C(OCCCOCCCOCC(N[C@@H](C(C)(C)C)C(N5[C@H](C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)C[C@@H](O)C5)=O)=O)C=C4F
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : ≥ 100 mg/mL (102.55 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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)
Purity & Documentation
-
Data Sheet (279 KB)
-
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)
-
Handling Instructions (2659 KB)
References
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 | 1.0255 mL | 5.1273 mL | 10.2546 mL | 25.6366 mL |
| 5 mM | 0.2051 mL | 1.0255 mL | 2.0509 mL | 5.1273 mL | |
| 10 mM | 0.1025 mL | 0.5127 mL | 1.0255 mL | 2.5637 mL | |
| 15 mM | 0.0684 mL | 0.3418 mL | 0.6836 mL | 1.7091 mL | |
| 20 mM | 0.0513 mL | 0.2564 mL | 0.5127 mL | 1.2818 mL | |
| 25 mM | 0.0410 mL | 0.2051 mL | 0.4102 mL | 1.0255 mL | |
| 30 mM | 0.0342 mL | 0.1709 mL | 0.3418 mL | 0.8546 mL | |
| 40 mM | 0.0256 mL | 0.1282 mL | 0.2564 mL | 0.6409 mL | |
| 50 mM | 0.0205 mL | 0.1025 mL | 0.2051 mL | 0.5127 mL | |
| 60 mM | 0.0171 mL | 0.0855 mL | 0.1709 mL | 0.4273 mL | |
| 80 mM | 0.0128 mL | 0.0641 mL | 0.1282 mL | 0.3205 mL | |
| 100 mM | 0.0103 mL | 0.0513 mL | 0.1025 mL | 0.2564 mL |
AZ'6421 Related Classifications
HY-135312 Related Classifications
Powered by Bioz