PROTAC PI3Kα degrader-1
Based on 1 Customer Validation
PROTAC PI3Kα degrader-1 is a PI3Kα PROTAC degrader that recruits CRBN, with a DC50 of 0.08 μM in T47D breast cancer cells. PROTAC PI3Kα degrader-1 inhibits the phosphorylation of AKT at the Ser473 site in cancer cells and exhibits in vivo anticancer efficacy in xenograft models. PROTAC PI3Kα degrader-1 can be used in cancer-related research.
(Pink: PI3Kα ligand (HY-174798); Blue: Cereblon ligand (HY-10984); Black: linker).
For research use only. We do not sell to patients.
- Purity: 99.21%
- Formula: C46H49F2N7O8S
- Molecular Weight:897.99
-
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
Description
IC50 & Target
[1]|
PI3Kα 0.08 μM (DC50) |
PI3Kα 62 nM (IC50) |
PI3Kβ 293.94 nM (IC50) |
PI3Kγ > 10000 nM (IC50) |
PI3Kδ 42.10 nM (IC50) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| T47D | DC50 |
0.08 μM
|
Degradation of PI3Kα in human T47D breast cancer cells assessed via Western blot after 24 h incubation.
Degradation of PI3Kα in human T47D breast cancer cells assessed via Western blot after 24 h incubation.
|
40518729 |
| T47D | IC50 |
0.35 μM
|
Antiproliferative activity against human T47D breast cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human T47D breast cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
| MDA-MB-453 | IC50 |
1.64 μM
|
Antiproliferative activity against human MDA-MB-453 cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human MDA-MB-453 cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
| HGC-27 | IC50 |
1.45 μM
|
Antiproliferative activity against human HGC-27 gastric cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human HGC-27 gastric cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
| AGS | IC50 |
0.37 μM
|
Antiproliferative activity against human AGS gastric cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human AGS gastric cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
| LNCaP | IC50 |
3.38 μM
|
Antiproliferative activity against human LNCaP prostate cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human LNCaP prostate cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
| PC-3 | IC50 |
1.48 μM
|
Antiproliferative activity against human PC3 prostate cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human PC3 prostate cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
| Pfeiffer | IC50 |
0.69 μM
|
Antiproliferative activity against human Pfeiffer cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
Antiproliferative activity against human Pfeiffer cancer cells assessed as reduction in cell viability incubated for 3 days by MTT or CTG assay.
|
40518729 |
In Vitro
PROTAC PI3Kα degrader-1 (compound 12) inhibits the proliferation of various cancer cell lines, with IC50 values ranging from 0.35 μM (T47D) to 3.38 μM (LNCaP)[1].
PROTAC PI3Kα degrader-1 inhibits purified PI3Kα enzyme with an IC50 of 81 nM[1].
PROTAC PI3Kα degrader-1 inhibits purified PI3Kα, PI3Kβ and PI3Kδ enzymes with IC50 values of 62 nM, 293.94 nM and 42.10 nM, respectively, and exhibits high selectivity for PI3Kγ (IC50 > 104 nM)[1].
PROTAC PI3Kα degrader-1 (1 μM) exhibits excellent kinase selectivity, potently inhibiting PIK3CA with negligible activity against the other 79 tested kinases[1].
PROTAC PI3Kα degrader-1 (0.0032-10 μM; 24 h) potently and selectively degrades PI3Kα in T47D breast cancer cells, with a DC50 of 0.08 μM. The degradation initiates at 4 h, reaches a peak at 24 h, and has a half-life of 8.6 h[1].
PROTAC PI3Kα degrader-1 (0.001-10 μM; 24 h) degrades PI3Kα in HGC-27 gastric cancer cells in a concentration- and time-dependent manner. Its degradation process initiates at 4 h, reaches a peak at 24 h, and has a half-life of 4.5 h[1].
PROTAC PI3Kα degrader-1 (0.0032-10 μM; 24 h) inhibits phosphorylation of AKT Ser473 in a concentration-dependent manner in T47D breast cancer cells and HGC-27 gastric cancer cells[1].
PROTAC PI3Kα degrader-1 (1 μM; 8-56 h) degrades PI3Kα in T47D breast cancer cells via the CRBN-mediated ubiquitin-proteasome pathway, without affecting PIK3CA mRNA levels, and the expression of PI3Kα is recoverable 48 h after removal of this compound[1].
PROTAC PI3Kα degrader-1 (30-60 min at 37 °C) exhibits excellent stability in mouse, rat, dog, monkey and human plasma[1].
PROTAC PI3Kα degrader-1 (incubated at 37 °C for 30-60 min) exhibits moderate to high levels of clearance in mouse, rat, dog, monkey and human liver microsomes, with a half-life ranging from 22.6 min (mouse) to 67.6 min (dog), and its metabolism is dependent on NADPH[1].
PROTAC PI3Kα degrader-1 (10 μM) exhibits favorable cardiac safety, with extremely weak inhibitory effect on hERG channels (10.19% at 10 μM), and negligible cytotoxicity in AC16 cardiomyocytes (IC50 > 50 μM). Its selectivity index is over 140-fold higher than that in T47D cells[1].
PROTAC PI3Kα degrader-1 (0.1-10 μM; 24 h) induces concentration-dependent G2/M cell cycle arrest in T47D breast cancer cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:T47D breast cancer cells
-
Concentration:0.0032, 0.016, 0.08, 0.4, 2, 10 μM
-
Incubation Time:1, 2, 4, 8, 12, 24 h
-
Result:Induced concentration-dependent degradation of PI3Kα with a DC50 of 0.08 μM.
Induced time-dependent degradation, initiating at 4 h and reaching maximum by 24 h, with a calculated half-life (t1/2) of 8.6 h.
-
Cell Line:HGC-27 gastric cancer cells
-
Concentration:0.001, 0.01, 0.1, 0.5, 1, 10 h
-
Incubation Time:1, 2, 4, 8, 12, 24 h
-
Result:Induced concentration-dependent degradation of PI3Kα.
Induced time-dependent degradation, initiating at 4 h and reaching maximum by 24 h, with a calculated half-life (t1/2) of 4.5 h.
-
Cell Line:T47D breast cancer cells, HGC-27 gastric cancer cells
-
Concentration:0.0032, 0.016, 0.08, 0.4, 2, 10 μM (T47D); 0.001, 0.01, 0.1, 0.5, 1, 10 h (HGC-27)
-
Incubation Time:24 h
-
Result:Suppressed phosphorylation of AKT at the Ser473 site in a concentration-dependent manner, correlating with PI3Kα degradation in both cell lines.
-
Cell Line:T47D breast cancer cells
-
Concentration:0.1, 1, 10 μM
-
Incubation Time:24 h
-
Result:Induced concentration-dependent G2/M phase cell cycle arrest.
Parmacokinetics
| Species | Dose | Route | T1/2β | MRT0-t | AUC0-t | Cmax | F |
|---|---|---|---|---|---|---|---|
| Mice[1] | 3.0 mg/kg | i.v. | 7.88 h | 6.69 h | 12708.04 ng/mL·h | / | / |
| Mice[1] | 30 mg/kg | i.p. | >24 h | 10.7 h | 26312.5 ng/mL·h | 1423.33 ng/mL | 20 % |
| Rat[1] | 1.5 mg/kg | i.v. | 2.11 h | 1.98 h | 1120.01 ng/mL·h | / | / |
| Rat[1] | 15 mg/kg | i.p. | 4.28 h | 6.05 h | 5489.90 ng/mL·h | 554.67 ng/mL | 46.4 % |
In Vivo
PROTAC PI3Kα degrader-1 (30 mg/kg; i.p.; once daily for 21 consecutive days) exhibits potent in vivo anticancer activity in the DOHH2 lymphoma xenograft model, with a tumor growth inhibition (TGI) rate of 61.8% and shows good tolerance without significant body weight loss[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c nude mice (male, 20−22 g, gastric cancer xenograft model with HGC-27 cells inoculated under right flank, treatment initiated when average tumor volumes reached 100−300 mm3)[1]
-
Dosage:30 mg/kg; 60 mg/kg
-
Administration:i.p.; once daily for 14 days
-
Result:Achieved tumor growth inhibition (TGI) rates of 38.3% and 56.8% at the 30 mg/kg and 60 mg/kg doses, respectively.
Induced dose-dependent degradation of PI3Kα in tumor tissues.
Showed no significant body weight changes relative to vehicle controls.
-
Animal Model:BALB/c nude mice (male, 20−22 g, lymphoma xenograft model with DOHH2 tumor fragments inoculated under right flank, treatment initiated when average tumor volumes reached 100−300 mm3)[1]
-
Dosage:30 mg/kg
-
Administration:i.p.; once daily for 21 days
-
Result:Achieved a tumor growth inhibition (TGI) rate of 61.8%, which was superior to the positive controls Ibrutinib and Idelalisib.
Showed no significant body weight loss relative to vehicle controls.
Chemical Information
-
Appearance Solid
-
Molecular Weight 897.99
-
Formula C46H49F2N7O8S
-
Color Light yellow to yellow
-
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
-
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
In Vitro:
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)
Purity & Documentation
-
Data Sheet (287 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 | 1.1136 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
Powered by Bioz