dWBP4-1
dWBP4-1 (LC-04-118) is a CRBN-dependent molecular glue degrader targeting WBP4. dWBP4-1 binds to the IMiD site of CRBN via its glutarimide ring, induces the formation of the CRBN-WBP4 ternary complex (EC50 = 224 nM), and mediates the rapid degradation of WBP4 through the G-loop dependent ubiquitin-proteasome pathway, a process that can be rescued by MLN4924 (HY-70062), Lenalidomide (HY-A0003) or Bortezomib (HY-10227). dWBP4-1 causes almost no perturbation at the transcriptome and alternative splicing levels, exhibits no obvious cytotoxicity, and produces no hook effect. dWBP4-1 can be used for the construction of chemical genetic protein degradation platforms and research related to acute T-lymphoblastic leukemia.
For research use only. We do not sell to patients.
- Formula: C29H28N4O4
- Molecular Weight:496.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
dWBP4-1 (6 h) potently induces degradation of HiBiT-tagged WBP4 in MOLT-4 cells, with a DC50 of 3.4 nM[1].
dWBP4-1 (100 nM; 0.5-6 h) rapidly and dose-dependently induces the degradation of endogenous WBP4 in MOLT-4 cells, and this degradation effect depends on CRBN and the ubiquitin-proteasome pathway[1].
dWBP4-1 (1 μM; treatment for 1-24 h with 1 h pretreatment of Cycloheximide (HY-12320)) accelerates the degradation kinetics of endogenous WBP4 in HEK293T cells, and reduces the protein half-life when combined with Cycloheximide[1].
The CRBN-dependent degradation of endogenous WBP4 mediated by dWBP4-1 (1-1000 nM; 6 h) in HEK293T cells is strictly dependent on CRBN[1].
dWBP4-1 (1 μM; 6 h) exhibits excellent whole-proteome selectivity in MOLT-4 cells, as it specifically degrades WBP4 at a concentration of 1 μM without altering the levels of other IMiD targets or spliceosome proteins[1].
dWBP4-1 binds directly and specifically to CRBN with an IC50 of 378 nM[1].
dWBP4-1 induces the formation of the CRBN-dWBP4-1-WBP4 ternary complex, with an EC50 value of 224 nM[1].
Degradation of WBP4 induced by dWBP4-1 (6 h) in MOLT-4 cells depends on the G-loop region of the WW1 domain of WBP4, as the WBP4G146N mutation abolishes efficient degradation[1].
dWBP4-1 (1-10 μM) induces degradation of the WBP4 truncation-EGFP fusion protein in HEK293T cells, and a 41-amino-acid wTAG sequence serves as the minimal functional degron[1].
dWBP4-1 (0.17-10000 nM; 1-24 h) induces rapid, potent and monotonic degradation of N-terminal and C-terminal wTAG-fused BRD4-BD1 and PLK1 in HEK293T cells, with DC50 values ranging from 1.4 nM to 31 nM, and no hook effect is observed[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:wild-type MOLT-4 cells
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Concentration:100 nM (degradation time course); 1, 10, 100 and 1000 nM (6 h dose-response); 100 nM (rescue experiments)
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Incubation Time:0.5, 1, 1.5, 2, 2.5 h (100 nM); 6 h (1-1000 nM); 2 h (100 nM, with 1 h pretreatment of rescue agents)
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Result:Induced rapid WBP4 degradation detectable as early as 30 min post-treatment at 100 nM.
Induced dose-dependent degradation across 1-1000 nM after 6 h.
Pretreatment with 1 μM NEDD8-activating enzyme inhibitor, 10 μM cereblon modulatory agent, or 0.4 μM proteasome inhibitor completely rescued dWBP4-1-induced WBP4 degradation.
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Cell Line:wild-type HEK293T cells
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Concentration:1 μM
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Incubation Time:1, 2, 4, 8, 24 h (with 1 h Cycloheximide (HY-12320) pretreatment)
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Result:Significantly accelerated the rate of WBP4 protein loss compared to CHX alone, with WBP4 levels becoming undetectable by 8 h post-treatment.
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Cell Line:wild-type and CRBN-/- HEK293T cells
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Concentration:1, 10, 100 and 1000 nM
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Incubation Time:6 h
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Result:Induced dose-dependent WBP4 degradation in wild-type HEK293T cells, but this effect was completely abolished in CRBN-/- HEK293T cells.
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Cell Line:stable HEK293T cell lines expressing wTAG-fused oncoproteins (N-terminal wTAG-BRD4-BD1, N-terminal wTAG-PLK1, C-terminal BRD4-BD1-wTAG, C-terminal PLK1-wTAG)
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Concentration:1 μM (time course); 0.17, 0.5, 1.5, 4.6, 13.7, 14, 123, 370, 1111, 3333 and 10000 nM (dose-response: N-terminal fusions, C-terminal fusions)
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Incubation Time:1, 3, 6, 12, 24 h (1 μM); 3 h (N-terminal fusions dose-response); 6 h (C-terminal fusions dose-response)
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Result:Triggered rapid degradation of all wTAG-fused proteins, with near-complete clearance within hours.
N-terminal wTAG-BRD4-BD1 had a DC50 of 31 nM and Dₘₐₓ of 92%; N-terminal wTAG-PLK1 had a DC50 of 22 nM and Dₘₐₓ of 80%.
C-terminal BRD4-BD1-wTAG had a DC50 of 4.7 nM and Dₘₐₓ of 96%; C-terminal PLK1-wTAG had a DC50 of 1.4 nM and Dₘₐₓ of 84%.
All constructs showed monotonic dose-response profiles without a hook effect up to 10 μM.
Chemical Information
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Molecular Weight 496.56
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Formula C29H28N4O4
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SMILES
O=C1[C@@H](N2C(C(C=CC(C(N3CCN(CC3)CC4=C5C=CC=CC5=CC=C4)=O)=C6)=C6C2)=O)CCC(N1)=O
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Synonyms
LC-04-118
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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)