PROTAC PI3Kδ degrader-1
PROTAC PI3Kδ degrader-1 is a Lysine-targeted covalent PI3Kδ PROTAC degrader with a DC50 of 3.98 nM. PROTAC PI3Kδ degrader-1 has a potent antiproliferative activity and selective PI3Kδ inhibition (IC50: 8 nM). PROTAC PI3Kδ degrader-1 also significantly degrades p-AKT, induces cell cycle arrest in G1 phase and prompts cell apoptosis and autophagy. PROTAC PI3Kδ degrader-1 effectively inhibits the tumor growth in SU-DHL-6 xenograft mice model.
(Pink: PI3Kδ ligand (HY-169983); Blue: VHL ligand (HY-112078); Black: linker (HY-W013381)).
For research use only. We do not sell to patients.
- Formula: C63H79N11O8S
- Molecular Weight:1150.44
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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
All PROTACs Isoforms
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Biological Activity
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PI3Kδ 3.98 nM (DC50) |
PI3Kδ 8 nM (IC50) |
PI3Kα 589 nM (IC50) |
PI3Kβ >10000 nM (IC50) |
PI3Kγ 605 nM (IC50) |
PROTAC PI3Kδ degrader-1 (Compound B14) (0.001-10 μM, 72 h) has a potent antiproliferation activity against SU-DHL-6 and Pfeiffer cells (GI50: 0.17 and 0.35 μM, respectively)[1].
PROTAC PI3Kδ degrader-1 (10 mM, 0-48 h) has excellent stability with 80% remains After 48 h incubation[1].
PROTAC PI3Kδ degrader-1 (0.1-1 μM, 6-24 h) dose- and time-dependently degrades p-AKT and p110δ (DC50: 3.98 nM) in SU-DHL-6 cells[1].
PROTAC PI3Kδ (1-100 nM, 24 h) degrader-1 increases the ratio of LC3II /LC3I, booting up the autophagy in SU-DHL-6 cells[1].
PROTAC PI3Kδ degrader-1 (0.1-1 μM, 12 h) has a superior binding affinity to VHL ligase ligand, p110δ and p-AKT, and its two derivatives has a weaker antiproliferative activity compared to itself (GI50: 0.17 vs 0.90 and 0.87 μM)[1].
PROTAC PI3Kδ degrader-1 (100 nM, 12 h) degrades p110δ with a ubiquitin-proteasome pathways in SU-DHL-6 cells, and this effect is reversed by MLN4924 (HY-70062) (ubiquitination inhibitor) and MG132 (HY-13259) (proteasome inhibitor)[1].
PROTAC PI3Kδ degrader-1 selectively inhibits PI3Kδ (IC50: 8 nM), with > 70-fold selectivity for the other three isoforms (IC50s : >589 nM, respectively) in SU-DHL-6 cells[1].
PROTAC PI3Kδ degrader-1 (1-1000 nM, 24 h) has a strong degradation effect in p110δ but weak effect in p110α and p110β protein levels (DC50 > 1000 nM) and no degradation in p110γ in SU-DHL-6 cells[1].
PROTAC PI3Kδ degrader-1 (0.01-1 μM, 24 h) dose-dependently increases the proportion of cells in G1 phase and significantly induces cell death and damage in SU-DHL-6 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SU-DHL-6 cells
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Concentration:0.1, 1, 3, 10, 30, 100, 1000 nM
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Incubation Time:24 h
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Result:Effectively degraded the protein levels of p110δ and p-AKT at 100 and 1000 nM.
Induced the degradation of p110δ in a concentration-dependent manner, and the levels of p-AKT were lowered correspondingly.
Increased the ratio of LC3II /LC3I, booting up the autophagy.
exhibited much effective p110δ degradation activity with 58% and 65% degradation of p110δ at 100 and 1 000 nM.
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Cell Line:SU-DHL-6 cells
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Concentration:0.01, 0.1, 1 μM
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Incubation Time:24 h
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Result:Dose-dependently increased the proportion of cells in G1 phase.
Potently induced the cell cycle arrest at 0.1 μM compared that at 10 μM of Idelalisib (HY-13026).
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Cell Line:SU-DHL-6 cells
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Concentration:0.01, 0.1, 1 μM
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Incubation Time:24 h
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Result:Induced a significant amount of cell death and damage.
Induced much higher cell apoptotic percentages than that of Idelalisib with the same dose.
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 (4-6 weeks old) were injected subcutaneously with SU-DHL-6 cells (1× 107 cells/mouse)[1].
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Dosage:2, 10 mg/kg
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Administration:i.p., every 2 days for 21 days and then measured tumor size and body weight.
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Result:Exhibited remarkable antitumor efficacy with tumor growth inhibition of 59.1 and 73.3% at 2 and 10 mg/kg doses, respectively.
Induced no substantial toxic effects without significant body weight changes and death up to 10 mg/kg.
Significantly reduced p110δ protein levels, and dose-dependently decreased the expression of p-AKT.
Had a significant antiproliferative activity with reduction of Ki67 level.
Caused no obvious organ damage with normal morphology in the tissues of heart, liver, spleen, and kidneys.
Chemical Information
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Molecular Weight 1150.44
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Formula C63H79N11O8S
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SMILES
O=C([C@@H](NC(CCCCCCCCCN1CCC(C(N2CC[C@H](NC3=NC=NC4=CC=C(C5=CN=C(C(C(OC6=CC=CC=C6)=O)=C5)OC)N=C43)C2)=O)CC1)=O)C(C)(C)C)N7[C@@H](C[C@H](C7)O)C(N[C@H](C8=CC=C(C=C8)C9=C(N=CS9)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
[1]. Yuan B, et al. Lysine-Targeted Covalent Strategy Leading to the Discovery of Novel Potent PROTAC-Based PI3Kδ Degraders. J Med Chem. 2025 Jun 12; 68(11):11437-11467.Yuan B, et al. Lysine-Targeted Covalent Strategy Leading to the Discovery of Novel Potent PROTAC-Based PI3Kδ Degraders. J Med Chem. 2025 Jun 12; 68(11):11437-11467. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC PI3Kδ degrader-1 Related Classifications
HY-176239 Related Classifications
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