Cat. No.: HY-174469

PROTAC PI3K/110β degrader-2

PROTAC PI3K/110β degrader-2 is a VHL-recruiting PI3K/110β PROTAC degrader, with DC₅₀ values of 1.258 μM and 2.185 μM in MCF-7/ADM and A549/DDP cells, respectively. PROTAC PI3K/110β degrader-2 induces proteasomal degradation of PI3K/110β, inhibits phosphorylation of AKT and expression of Bcl-2, while suppressing the activity and expression of P-gp. It also induces endoplasmic reticulum stress and mitochondrial apoptosis via the PERK/CHOP pathway. PROTAC PI3K/110β degrader-2 exerts anti-tumor activity against multidrug-resistant cancer cells both in vitro and in vivo, and produces a synergistic effect when combined with Doxorubicin (HY-15142A) or Cisplatin (HY-17394), making it applicable for the research of multidrug-resistant cancers.

(Pink: PI3K ligand (HY-75124); Blue: VHL ligand (HY-125845); Black: linker (HY-W002042)).

For research use only. We do not sell to patients.

CAS No.: 3070438-79-5
Formula: C₅₁H₆₅N₉O₇S
Molecular Weight:948.18

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (295 KB)

PROTAC PI3K/110β degrader-2 Chemical Structure

CAS No.: 3070438-79-5

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

PROTAC PI3K/110β degrader-2 is a VHL-recruiting PI3K/110β PROTAC degrader, with DC₅₀ values of 1.258 μM and 2.185 μM in MCF-7/ADM and A549/DDP cells, respectively. PROTAC PI3K/110β degrader-2 induces proteasomal degradation of PI3K/110β, inhibits phosphorylation of AKT and expression of Bcl-2, while suppressing the activity and expression of P-gp. It also induces endoplasmic reticulum stress and mitochondrial apoptosis via the PERK/CHOP pathway. PROTAC PI3K/110β degrader-2 exerts anti-tumor activity against multidrug-resistant cancer cells both in vitro and in vivo, and produces a synergistic effect when combined with Doxorubicin (HY-15142A) or Cisplatin (HY-17394), making it applicable for the research of multidrug-resistant cancers^[1].
(Pink: PI3K ligand (HY-75124); Blue: VHL ligand (HY-125845); Black: linker (HY-W002042)).

IC₅₀ & Target

^[1]

PI3K

1.258 μM (DC₅₀, MCF-7/ADM)

PI3K

2.185 μM (DC₅₀, A549/DDP)

Bax

Bcl-2

Akt

All PROTACs Isoforms :

All PI3K Isoforms :

All Akt Isoforms :

All Bcl-2 Family Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
A549/CDDP	DC₅₀	2.19 μM	Half-maximal degradation of PI3K/p110β protein in human A549/DDP cells assessed via Western blot after 24 h treatment. Half-maximal degradation of PI3K/p110β protein in human A549/DDP cells assessed via Western blot after 24 h treatment.	40294240
A549	IC₅₀	85.2 μM	Antiproliferative activity against human A549 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay. Antiproliferative activity against human A549 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.	40294240
A549/CDDP	IC₅₀	39.23 μM	Antiproliferative activity against human A549/DDP cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay. Antiproliferative activity against human A549/DDP cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.	40294240
MCF7	IC₅₀	53.99 μM	Antiproliferative activity against human MCF-7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay. Antiproliferative activity against human MCF-7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.	40294240
MCF7	IC₅₀	38.73 μM	Antiproliferative activity against human MCF-7/ADM cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay. Antiproliferative activity against human MCF-7/ADM cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay.	40294240
MCF7	DC₅₀	1.258 μM	Selective degradation of p110β protein in human MCF-7/ADM multidrug-resistant breast cancer cells. Selective degradation of p110β protein in human MCF-7/ADM multidrug-resistant breast cancer cells.	40294240
A549/CDDP	DC₅₀	2.185 μM	Selective degradation of p110β protein in human A549/DDP multidrug-resistant lung cancer cells. Selective degradation of p110β protein in human A549/DDP multidrug-resistant lung cancer cells.	40294240
MCF7	IC₅₀	10.62 μM	Inhibition of cell viability in human MCF-7/ADM multidrug-resistant breast cancer cells incubated for 48 hrs by MTT assay. Inhibition of cell viability in human MCF-7/ADM multidrug-resistant breast cancer cells incubated for 48 hrs by MTT assay.	40294240
A549/CDDP	IC₅₀	18.75 μM	Inhibition of cell viability in human A549/DDP multidrug-resistant lung cancer cells incubated for 48 hrs by MTT assay. Inhibition of cell viability in human A549/DDP multidrug-resistant lung cancer cells incubated for 48 hrs by MTT assay.	40294240

In Vitro

PROTAC PI3K/110β degrader-2 (compound J-6) (2.5-25 μM) selectively degrades PI3K/p110β in MCF-7/ADM (DC₅₀ = 1.26 μM) and A549/DDP (DC₅₀ = 2.19 μM) cells in a time- and concentration-dependent manner via the proteasome and VHL E3 ligase pathways^[1].
PROTAC PI3K/110β degrader-2 (24 h) exhibits potent dose-dependent anti-tumor activity in vitro, with an IC₅₀ of 38.73 μM in multidrug-resistant MCF-7/ADM cells and an IC₅₀ of 39.23 μM in A549/DDP cells^[1].
PROTAC PI3K/110β degrader-2 (48 h) inhibits the viability of MCF-7/ADM cells and A549/DDP cells, with an IC₅₀ of 10.62 μM against the former and 18.75 μM against the latter^[1].
PROTAC PI3K/110β degrader-2 (6.25-25 μM; 24 h) inhibits the activity and expression of P-gp in MCF-7/ADM and A549/DDP cells, and exerts a strong synergistic anti-tumor effect with Cisplatin (HY-17394) in A549/DDP cells^[1].
PROTAC PI3K/110β degrader-2 (0.25-25 μM; 24 h) alters the mRNA expression of pten, akt and bcl-2 in A549/DDP cells^[1].
PROTAC PI3K/110β degrader-2 (6.25-100 μM; 24 h) inhibits the growth of A549/DDP cells, with a median effective dose of 38.203 μM^[1].
PROTAC PI3K/110β degrader-2 (0.25-25 μM; 24 h) induces endoplasmic reticulum stress-mediated mitochondrial apoptosis in MCF-7/ADM and A549/DDP cells by activating the UPR signaling pathway and regulating proteins of the AKT/Bcl-2 pathway^[1].
PROTAC PI3K/110β degrader-2 (6.25-25 μM; 24 h) dose-dependently induces the production of mitochondrial ROS in A549/DDP cells^[1].
PROTAC PI3K/110β degrader-2 (25 μM; 24 h) reduces the mitochondrial membrane potential of A549/DDP cells^[1].
PROTAC PI3K/110β degrader-2 (0.25-25 μM) regulates the expression of proteins related to apoptosis and the PI3K/AKT signaling pathway in A549/DDP cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Real Time qPCR^[1]

Cell Line:

A549/DDP multidrug-resistant lung cancer cells
Concentration:

25 μM
Incubation Time:

24 h
Result:

Increased pten、akt、bcl-2 mRNA expression in A549/DDP cells relative to untreated controls.

Cell Proliferation Assay^[1]

Cell Line:

A549/DDP multidrug-resistant lung cancer cells
Concentration:

6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM
Incubation Time:

24 h
Result:

Resulted in a growth inhibition in A549/DDP cells.
Achieved a median effect dose (D_m) of 38.203 μM, a dose-effect curve shape parameter (m) of 0.911, and a linear correlation coefficient (r) of 0.959.

Western Blot Analysis^[1]

Cell Line:

A549/DDP multidrug-resistant lung cancer cells
Concentration:

0.25, 2.5, 25 μM
Incubation Time:

24 h
Result:

Alters the mRNA expression of pten, akt and bcl-2.
Regulated the expression of proteins related to apoptosis and the PI3K/AKT signaling pathway.

In Vivo

J-6 (50 mg/kg; i.p.; once every other day; 7 doses) inhibits multidrug-resistant MCF-7/ADM xenograft tumor growth with high safety by selectively degrading PI3K/110β, activating endoplasmic reticulum stress-mediated mitochondrial apoptosis, and reducing P-gp expression^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

nude (implanted with MCF-7/ADM cells)^[1]
Dosage:

50 mg/kg
Administration:

i.p.; once every other day; 7 doses
Result:

Significantly reduced MCF-7/ADM xenograft tumor volume compared to the control group.
Effectively downregulated tumor tissue PI3K/110β level, with only a slight decrease in PI3K/110α levels.
Significantly increased tumor tissue expression of ATF6, CHOP, GRP78, and caspase-12, while slightly increasing P-PERK and P-IRE1 levels.
Significantly enhanced mitochondrial apoptosis markers cleaved-caspase-9 and Bax, while inhibiting cleaved-caspase-8 and Bcl-2.
Inhibited downstream PI3K signaling molecule p-AKT, with PTEN levels similar to controls.
Dramatically reduced P-gp expression in tumor tissues.
Caused no significant change in mouse body weight, with organ index, major organ hematoxylin and eosin staining, and serum biochemical parameters (PLT, WBC, LYM, ALT, AST, CR, BUN) all within normal ranges.

Chemical Information

CAS No. 3070438-79-5
Molecular Weight 948.18
Formula C₅₁H₆₅N₉O₇S
SMILES

O=C(NCC1=CC=C(C=C1)C2=C(N=CS2)C)[C@H]3N(C[C@@H](C3)O)C([C@H](C(C)(C)C)NC(CCCCCCNC(C4=CC=CC=C4NC(C)C5=CC(C)=CN6C5=NC(N7CCOCC7)=CC6=O)=O)=O)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (295 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Cen J, et al. Double Swords in One: Novel Selective PI3K/110β PROTAC Degraders for the Treatment of Multidrug-Resistant Cancer by Activating ERS and Inhibiting P-gp. J Med Chem. 2025 May 8;68(9):9446-9464. [Content Brief]

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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PROTAC PI3K/110β degrader-2

All PROTACs Isoforms

All PI3K Isoforms

All Akt Isoforms

All Bcl-2 Family Isoforms