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PI3KAD-Deg-5 | PI3KAD-Deg-5 : Degrader (PROTAC) of PIK3CA, PIK3CD
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
PIK3CA
  • IC50:0.34 nM
  • DC50:0.05 nM
  • IC50:0.06 nM
  • IC50:2.65 nM
PIK3CD
  • IC50:1.85 nM
    up to 100 nM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    Whole-proteome analysis demonstrated that PI3Kα was significantly degraded by D5 in T47D cells, but ...
    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    >10,000-fold degradation selectivity over the PI3Kβ and PI3Kγ isoforms

    Potency
    Cellular
    In Vitro

    PIK3CA

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.5c03368

    PIK3CD

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.5c03368

    In Vivo Validations

    Rat
    Dose: 1 mg/Kg
    Route of delivery: Intravenous
    Plasma half life: 4.43 h
    Systemic clearance: 1.99 L/h/Kg
    Cmax: 4612.84 ng/mL
    Area Under the Curve:: 510.26 h*ng/mL

    DOI Reference: 10.1021/acs.jmedchem.5c03368

    Dose: 10 mg/Kg
    Route of delivery: Oral
    Plasma half life: 1.66 h
    Systemic clearance: 108.80 L/h/Kg
    Cmax: 17.30 ng/mL
    Tmax: 1.44 h
    Area Under the Curve:: 94.26 h*ng/mL
    Bioavailability: 1.85%

    DOI Reference: 10.1021/acs.jmedchem.5c03368

    Negative Control Compounds

    D5Me
    Notes: D5Me not degraded the PI3Kα protein
    SMILES: COC1=C2C(C3=NCCN3C(NC(C4=CN=C(N)N=C4)=O)=N2)=CC=C1OCCCN5CCN(CCCCCCCC(NC6=C(C(N(C7CCC(N(C)C7=O)=O)C8)=O)C8=CC=C6)=O)CC5

    Chemical Information

    Molecular Formula C45H56N12O7
    SMILEs COc1c(OCCCN2CCN(CCCCCCCCC(=O)Nc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4)CC2)ccc2c1N=C(NC(=O)c1cnc(N)nc1)N1CCN=C21
    InChI InChI=1S/C45H56N12O7/c1-63-39-34(15-13-31-38(39)52-45(56-20-17-47-40(31)56)53-41(60)30-26-48-44(46)49-27-30)64-25-9-19-55-23-21-54(22-24-55)18-7-5-3-2-4-6-12-35(58)50-32-11-8-10-29-28-57(43(62)37(29)32)33-14-16-36(59)51-42(33)61/h8,10-11,13,15,26-27,33H,2-7,9,12,14,16-25,28H2,1H3,(H,50,58)(H2,46,48,49)(H,51,59,61)(H,52,53,60)
    Molecular weight 876.44 Da
    AlogP 3.0776000000000048
    HBond acceptors 19
    HBond donors 5
    Atoms 120

    References

    Publications

    Cross References

    canSAR: 7719224 PubChem: 177924597

    Expert Reviews

    by SERP
    (on 22 Apr 2026)
    Cellular Use Rating
    In Model Organisms
    PI3KAD-Deg-5 is well profiled, highly potent and selective PI3Kα/δ degrader. While PI3Kα DC50 is in the sub nM range, PI3Kα/δ DC50 hasn't been determined (but seems comparable to PI3Kα in SKBR3 cells)....
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