PROTAC PI3K/110β degrader-1
PROTAC PI3K/110β degrader-1 is a VHL-recruiting PROTAC degrader targeting PI3K/110β, with DC50 values of 0.416 μM (MCF-7) and 19.66 μM (A549), respectively. PROTAC PI3K/110β degrader-1 recruits VHL to induce proteasomal degradation of PI3K/110β. It activates endoplasmic reticulum stress (ERS)-mediated mitochondrial apoptosis via the PERK/ATF4/CHOP unfolded protein response (UPR) pathway, downregulates p-AKT and Bcl-2, upregulates Bax, cleaved-caspase-9 and cleaved-caspase-3, inhibits the expression and activity of P-gp, and exerts synergistic anti-tumor effects with Doxorubicin (Adriamycin, ADM) (HY-15142A) and Cisplatin (DDP) (HY-17394). PROTAC PI3K/110β degrader-1 can be used in research related to multidrug-resistant cancers.
(Pink: PI3K and p110β ligand (HY-75124); Blue: VHL ligand (HY-125845); Black: linker (HY-W040168)).
For research use only. We do not sell to patients.
- CAS No.: 3070438-85-3
- Formula: C51H65N9O9S
- Molecular Weight:980.18
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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Bax |
Caspase-9 |
Caspase-3 |
Bcl-2 |
Akt |
PI3K |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MCF7 | DC50 |
1.26 μM
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Degradation of PI3K p110β protein in human MCF-7/ADM multidrug-resistant cancer cells after 24 h incubation, measured via Western blot analysis.
Degradation of PI3K p110β protein in human MCF-7/ADM multidrug-resistant cancer cells after 24 h incubation, measured via Western blot analysis.
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40294240 |
| MCF7 | IC50 |
30.15 μM
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Cytotoxicity against human MCF-7/ADM multidrug-resistant cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human MCF-7/ADM multidrug-resistant cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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40294240 |
| MCF7 | IC50 |
33.88 μM
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Cytotoxicity against human MCF-7 cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human MCF-7 cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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40294240 |
| A549/CDDP | IC50 |
43.12 μM
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Cytotoxicity against human A549/DDP multidrug-resistant cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human A549/DDP multidrug-resistant cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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40294240 |
| A549 | IC50 |
75.3 μM
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Cytotoxicity against human A549 cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
Cytotoxicity against human A549 cancer cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.
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40294240 |
| MCF7 | DC50 |
0.416 μM
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Degradation of p110β protein in human MCF-7/ADM multidrug-resistant cancer cells assessed via immunoblotting analysis.
Degradation of p110β protein in human MCF-7/ADM multidrug-resistant cancer cells assessed via immunoblotting analysis.
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40294240 |
| A549/CDDP | DC50 |
19.66 μM
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Degradation of p110β protein in human A549/DDP multidrug-resistant cancer cells assessed via immunoblotting analysis.
Degradation of p110β protein in human A549/DDP multidrug-resistant cancer cells assessed via immunoblotting analysis.
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40294240 |
| MCF7 | DC50 |
3.876 μM
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Degradation of p110α protein in human MCF-7/ADM multidrug-resistant cancer cells assessed via immunoblotting analysis.
Degradation of p110α protein in human MCF-7/ADM multidrug-resistant cancer cells assessed via immunoblotting analysis.
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40294240 |
| A549/CDDP | DC50 |
28.4 μM
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Degradation of p110α protein in human A549/DDP multidrug-resistant cancer cells assessed via immunoblotting analysis.
Degradation of p110α protein in human A549/DDP multidrug-resistant cancer cells assessed via immunoblotting analysis.
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40294240 |
| MCF7 | IC50 |
8.30 μM
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Inhibition of cell viability in human MCF-7/ADM multidrug-resistant cancer cells incubated for 48 h by MTT assay.
Inhibition of cell viability in human MCF-7/ADM multidrug-resistant cancer cells incubated for 48 h by MTT assay.
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40294240 |
| A549/CDDP | IC90 |
17.04 μM
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Inhibition of cell viability in human A549/DDP multidrug-resistant cancer cells incubated for 48 h by MTT assay.
Inhibition of cell viability in human A549/DDP multidrug-resistant cancer cells incubated for 48 h by MTT assay.
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40294240 |
PROTAC PI3K/110β degrader-1 (compound J-9) (2.5-25 μM; 24 h) induces time- and concentration-dependent proteasome-mediated degradation of PI3K p110β in multidrug-resistant cancer cells MCF-7/Doxorubicin (Adriamycin, ADM) (HY-15142A) and A549/Cisplatin (DDP) (HY-17394), with DC50 values of 0.416 μM (MCF-7/ADM) and 19.66 μM (A549/DDP), respectively[1].
PROTAC PI3K/110β degrader-1 (6.25-25 μM; 24 h) inhibits the activity and expression of P-gp in MCF-7/ADM and A549/DDP multidrug-resistant cancer cells by reducing Na+/K+-ATPase activity and inducing proteasome-mediated downregulation of P-gp[1].
PROTAC PI3K/110β degrader-1 (48 h) exerts strong synergistic anti-tumor effects with Adriamycin in MCF-7/ADM multidrug-resistant cancer cells[1].
PROTAC PI3K/110β degrader-1 (25 μM; 24 h) downregulates the mRNA expression of bcl-2, pten and akt in MCF-7/ADM cells[1].
As a single agent, PROTAC PI3K/110β degrader-1 (6.25-100 μM; 24 h) inhibits the proliferation of MCF-7/ADM cells (Dm = 20.625 μM), and suppresses cell proliferation in combination with ADM (Dm = 28.203 μM)[1].
PROTAC PI3K/110β degrader-1 (6.25-25 μM; 24 h) induces endoplasmic reticulum stress-mediated mitochondrial apoptosis in MCF-7/ADM and A549/DDP multidrug-resistant cancer cells by regulating the AKT/Bcl-2 signaling pathway and activating the PERK/CHOP unfolded protein response pathway[1].
PROTAC PI3K/110β degrader-1 (6.25-25 μM; 24 h) induces dose-dependent mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential depolarization in MCF-7/ADM cells[1].
PROTAC PI3K/110β degrader-1 (0.25-25 μM) regulates the expression of pro-apoptotic, anti-apoptotic and endoplasmic reticulum stress-related proteins in MCF-7/ADM cells in a concentration-dependent manner in vitro, and the degradation of p110β depends on the proteasome and VHL pathways[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7/ADM, A549/DDP
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Concentration:2.5, 25 μM
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Incubation Time:24 h
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Result:Induced concentration-dependent degradation of PI3K p110β in both cell lines, with DC50 values of 0.416 μM (MCF-7/ADM) and 19.66 μM (A549/DDP), respectively.
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Cell Line:MCF-7, MCF-7/ADM, A549, A549/DDP
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Concentration:Multiple concentrations
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Incubation Time:48 h
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Result:Exhibited dose-dependent cytotoxicity across all tested cell lines, with the lowest IC50 values observed in multidrug-resistant cell lines.
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Cell Line:MCF-7/ADM
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Concentration:25 μM
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Incubation Time:24 h
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Result:Reduced relative mRNA expression of bcl-2, pten and akt in MCF-7/ADM cells relative to control.
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Cell Line:MCF-7/ADM
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Concentration:6.25, 12.5, 25, 50, 100 μM
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Incubation Time:24 h
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Result:Inhibited MCF-7/ADM cell growth as a single agent with a median effect dose (Dm) of 20.625 μM, a dose-effect curve shape parameter (m) of 0.6731, and a linear correlation coefficient (r) of 0.986.
Inhibited MCF-7/ADM cell growth in combination with ADM with a median effect dose (Dm) of 28.203 μM, a dose-effect curve shape parameter (m) of 0.911, and a linear correlation coefficient (r) of 0.959.
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Cell Line:MCF-7/ADM, A549/DDP
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Concentration:0.04, 0.2, 1, 5, 25, 50 μM
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Incubation Time:24 h
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Result:Reduced p110α levels in both cell lines.
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Cell Line:MCF-7/ADM, A549/DDP
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Concentration:25 μM
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Incubation Time:24 h
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Result:Induced apoptosis in both cell lines
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Cell Line:MCF-7/ADM, A549/DDP
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Concentration:0.25, 2.5, 25 μM
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Incubation Time:24 h
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Result:Increased P-PERK, ATF4, CHOP, GRP78, caspase-12, Bax, cleaved-caspase-9, cleaved-caspase-3, CytC; decreased p-AKT, Bcl-2, caspase-8.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice[1]
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Dosage:50 mg/kg
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Administration:i.p.; once every other day; 7 doses
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Result:Significantly reduced MCF-7/ADM xenograft tumor volume and weight compared to control group.
Effectively downregulated PI3K/110β and PI3K/110α protein levels in tumor tissues.
Increased expression of endoplasmic reticulum stress-related proteins ATF6, CHOP, GRP78, and caspase-12.
Enhanced mitochondrial apoptosis markers including cleaved-caspase-9 and Bax, while inhibiting cleaved-caspase-8 and Bcl-2.
Inhibited downstream p-AKT signaling and dramatically reduced P-glycoprotein (P-gp) expression in tumor tissues.
Caused no significant changes in mouse body weight during treatment.
Maintained organ index, hematoxylin and eosin (H&E) staining of major organs, and serum biochemical markers (PLT, WBC, LYM, ALT, AST, CR, BUN) within normal ranges.
Chemical Information
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CAS No. 3070438-85-3
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Molecular Weight 980.18
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Formula C51H65N9O9S
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SMILES
O=C(NCC1=CC=C(C=C1)C2=C(N=CS2)C)[C@H]3N(C[C@@H](C3)O)C([C@@H](NC(CCOCCOCCNC(C4=CC=CC=C4NC(C)C5=CC(C)=CN6C5=NC(N7CCOCC7)=CC6=O)=O)=O)C(C)(C)C)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC PI3K/110β degrader-1 Related Classifications
HY-176421 Related Classifications
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