FDU73
FDU73 is a potent and selective BTK PROTAC degrader with a DC50 value of 2.9 nM (JeKo-1). FDU73 degrades BTK via the ubiquitin-proteasome system. FDU73 exerts antiproliferative effects on cancer cells. FDU73 can be used for the research of B-cell malignancies.
(Pink: Btk ligand (HY-173126); Blue: Cereblon ligand (HY-173378); Black: linker (HY-168297)).
For research use only. We do not sell to patients.
- Formula: C48H55N9O5
- Molecular Weight:838.01
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
FDU73 (Compound 27) (0.01 nM-1 μM; 1-24 h) potently induces concentration- and time-dependent degradation of BTK in JeKo-1 cells, with a DC50 of 2.9 nM, and achieves complete degradation at a concentration of 100 nM after 4 h of treatment[1].
FDU73 (0.1 nM-1 μM; 24 h) potently induces concentration-dependent degradation of wild-type and BTKC481S mutant BTK in TMD8 cells, with DC50 values of 2.8 nM and 4.3 nM, respectively[1].
FDU73 (10 nM; 24 h) induces BTK degradation in JeKo-1 cells via the ubiquitin-proteasome system in a CRBN- and proteasome-dependent manner[1].
FDU73 (0.1 nM-1 μM; 8 h) selectively induces BTK degradation in JeKo-1 cells without affecting the novel CRBN substrates IKZF1, IKZF3 or GSPT1[1].
FDU73 (100 nM; 4 h) exhibits proteome-wide selectivity for BTK degradation in JeKo-1 cells, with only BTK, CSK and BLK showing significant downregulation at 100 nM for 4 h[1].
FDU73 potently inhibits the proliferation of TMD8 BTKWT cells with an IC50 of 9.9 nM, and also exhibits potent activity against TMD8 BTKC481S mutant cells[1].
FDU73 exhibits excellent metabolic stability in mouse liver microsomes, with a half-life of over 145 min[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:JeKo-1 cells
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Concentration:0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM (24 h incubation); 100 nM (time-dependent analysis)
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Incubation Time:24 h (concentration-dependent analysis); 1 h, 2 h, 4 h, 8 h, 12 h, 24 h (time-dependent analysis)
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Result:Induced concentration-dependent BTK degradation with a DC50 of 2.9 nM, achieving complete BTK depletion at 30 nM with no observed hook effect up to 1 μM.
Achieved significant BTK reduction at 1 h, with complete degradation achieved by 4 h in time-dependent assays.
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Cell Line:TMD8 BTKWT and TMD8 BTKC481S cells
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:24 h
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Result:Induced concentration-dependent degradation of wild-type BTK with a DC50 of 2.8 nM in TMD8 BTKWT cells.
Induced concentration-dependent degradation of C481S mutant BTK with a DC50 of 4.3 nM in TMD8 BTKC481S cells.
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Cell Line:JeKo-1 cells
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Concentration:10 nM, 30 nM, 100 nM (FDU73N); 10 nM (FDU73, following 2 h pretreatment with 2 μM MLN-4924 or 20 μM proteasome inhibitor bortezomib)
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Incubation Time:24 h (FDU73N); 24 h (FDU73, following 2 h pretreatment)
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Result:Failed to reduce BTK protein levels at concentrations up to 100 nM for CRBN-binding defective negative control FDU73N.
Significantly diminished FDU73-induced BTK degradation when JeKo-1 cells were pretreated with MLN-4924 (HY-70062) or proteasome inhibitor Bortezomib (HY-10227).
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Cell Line:JeKo-1 cells
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:8 h
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Result:Downregulated BTK protein levels in a dose-dependent manner.
Exerted no effect on the protein levels of CRBN neo-substrates IKZF1, IKZF3, and GSPT1 at all tested concentrations.
Chemical Information
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Molecular Weight 838.01
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Formula C48H55N9O5
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SMILES
O=C(N[C@@H]1C[C@@H](NC2=C3C(NC=C3C(C4=CC=C(OC5=CC=CC=C5)C=C4)=O)=NC=N2)CC1)CC6CCN(CCC7CCN(C8=NC=C(C(CC9)C(NC9=O)=O)C=C8)CC7)CC6
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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)