PROTAC PI3Kα degrader-1
Based on 1 Customer Validation
PROTAC PI3Kα degrader-1 is a PI3Kα PROTAC degrader (DC50 = 0.08 μM), demonstrating good selectivity for PI3Kα degradation over PI3Kβ, PI3Kγ, and PI3Kδ. PROTAC PI3Kα degrader-1 effectively degrades PI3Kα in a time- and concentration-dependent, over PI3Kβ, PI3Ky and PI3Kδ, and potently inhibited the phosphorylation of AKT at the Ser473site. PROTAC PI3Kα degrader-1 shows significant in vivo anticancer efficacy in HGC-27 and DOHH2 xenograft models.
(Pink: PI3Kα ligand (HY-174798); Blue: Cereblon ligand (HY-10984); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.21%
- Fòrmula: C46H49F2N7O8S
- Peso molecular:897.99
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Almacenamiento: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]
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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
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Actividad biológica
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Cereblon |
PI3Kα 62 nM (IC50) |
PI3Kβ 293.94 nM (IC50) |
PI3Kγ >10000 nM (IC50) |
PI3Kδ 42.10 (IC50) |
PROTAC PI3Kα degrader-1 (Compound 12) (1 μM) shows negligible activity against 79 kinases (< 20% inhibition) while exhibits potent inhibition of PIK3CA (＞ 95%) in T47D breast cancer cells[1].
PROTAC PI3Kα degrader-1 (0.1-10 μM) demonstrates good selectivity for PI3Kα degradation over PI3Kβ, PI3Kγ and PI3Kδ in T47D breast cancer cells[1].
PROTAC PI3Kα degrader-1 exhibits excellent selectivity for the degradation of PI3Kα in various cancer cell lines, with IC50s of 0.35 μM (T47D), 1.64 μM (MDA-MB-453), 1.45 μM (HGC-27), 0.37 μM (AGS), 3.38 μM (LNCaP), 1.48 μM (PC3) and 0.69 μM (Pfeiffer)[1].
PROTAC PI3Kα degrader-1 (0.0032-10 μM, 0-24 h) degrades PI3Kα in a concentration- and time-dependent manner in T47D and HGC-27 cells[1].
PROTAC PI3Kα degrader-1 (1 μM, 20 h) degrades PI3Kα via the ubiquitin-proteasome pathway through CRBN recruitment in T47D cells[1].
PROTAC PI3Kα degrader-1 (0.1-10 μM, 24 h) induces cell cycle arrest at the G2/M phase concentration-dependently in T47D cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:T47D cells
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Concentration:1 μM
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Incubation Time:20h with/without MG132 (HY-13259) (1 μM)
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Result:Reduced the level of PI3Kα, while the addition of MG132 restored PI3Kα levels.
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Cell Line:T47D cells
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Concentration:1 μM
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Incubation Time:24 h
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Result:Did not decrease the mRNA levels of PIK3CA.
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Cell Line:T47D cells
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Concentration:1 μM
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Incubation Time:8 h after Thalidomide (HY-14658) (10 μM) preincubated 1h and then incubated in fresh medium for an additional 48 hours.
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Result:Degraded PI3Kα but preincubation with thalidomide (10 μM, 1 h) reduced this degradation.
Restored PI3Kα expression to normal levels 48 h after an 8h treatment followed by incubation in fresh medium.
PROTAC PI3Kα degrader-1 (Compound 12) (2 μM, 0-60 min) shows superior plasma stability across all of the tested species including mice, rats, dogs, monkeys, and human[1].
PROTAC PI3Kα degrader-1 (2 μM, 0-60 min) exhibits moderate to high clearance rates in each species,with half-life (t1/2) values of 22.6 min (mouse), 45.7 min (rat), 67.6 min (dog), 32.5 min (monkey), and 34.7 min (human), which is heavily dependent on NADPH[1].
PROTAC PI3Kα degrader-1 (30-60 mg/kg, i.p., daily for 14 days) demonstrates significant anticancer efficacy in the HGC-27 xenograft model[1].
PROTAC PI3Kα degrader-1 (30 mg/kg, i.p., daily for 21 days) exhibits potent antitumor activity in the DOHH2 xenograft model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male BALB/c nude mice (20-22 g) bearing HGC-27 xenografts[1]
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Dosage:30, 60 mg/kg
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Administration:i.p. daily for 14 days
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Result:Showed tumor growth rates (TGI) of 38.3% at 30 mg/kg and 56.8% at 60 mg/kg.
Induced dose-dependent degradation of PI3Kα.
Showed no significant changes in body weight.
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Animal Model:Male BALB/c nude mice (20-22 g) bearing DOHH2 xenografts[1]
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Dosage:30 mg/kg
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Administration:i.p. daily for 21 days
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Result:Demonstrated a strong efficacy with a tumor growth inhibition (TGI) rate of 61.8%, which is more effective than Ibrutinib (HY-10997) administered orally at a dose of 25 mg/kg and Idelalisib (HY-13026) administered orally at a dose of 10 mg/kg.
Showed no significant body weight loss.
Chemical Information
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Appearance Solid
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Peso molecular 897.99
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Fòrmula C46H49F2N7O8S
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Color Light yellow to yellow
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SMILES
O=S(NC1=C(N=CC(C2=CC3=C(N=CN=C3C(OCCCCCCCCCCCCNC4=CC=CC(C(N5C6CCC(NC6=O)=O)=O)=C4C5=O)=C2)C)=C1)OC)(C7=CC=C(C=C7F)F)=O
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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
Solvente y solubilidad
DMSO : 100 mg/mL (111.36 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)
Pureza y Documentación
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Ficha de datos (279 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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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 |
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| DMSO | 1 mM | 1.1136 mL | 5.5680 mL | 11.1360 mL | 27.8400 mL |
| 5 mM | 0.2227 mL | 1.1136 mL | 2.2272 mL | 5.5680 mL | |
| 10 mM | 0.1114 mL | 0.5568 mL | 1.1136 mL | 2.7840 mL | |
| 15 mM | 0.0742 mL | 0.3712 mL | 0.7424 mL | 1.8560 mL | |
| 20 mM | 0.0557 mL | 0.2784 mL | 0.5568 mL | 1.3920 mL | |
| 25 mM | 0.0445 mL | 0.2227 mL | 0.4454 mL | 1.1136 mL | |
| 30 mM | 0.0371 mL | 0.1856 mL | 0.3712 mL | 0.9280 mL | |
| 40 mM | 0.0278 mL | 0.1392 mL | 0.2784 mL | 0.6960 mL | |
| 50 mM | 0.0223 mL | 0.1114 mL | 0.2227 mL | 0.5568 mL | |
| 60 mM | 0.0186 mL | 0.0928 mL | 0.1856 mL | 0.4640 mL | |
| 80 mM | 0.0139 mL | 0.0696 mL | 0.1392 mL | 0.3480 mL | |
| 100 mM | 0.0111 mL | 0.0557 mL | 0.1114 mL | 0.2784 mL |
PROTAC PI3Kα degrader-1 Related Classifications
HY-174461 Related Classifications
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