PROTAC BCL6/IKZF1/3 Degrader-1
PROTAC BCL6/IKZF1/3 Degrader-1 is an orally active bifunctional PROTAC‑IMiD protein degrader that targets and degrades BCL6, IKZF1 and IKZF3. PROTAC BCL6/IKZF1/3 Degrader-1 induces ubiquitination and proteasome-mediated degradation of target proteins by recruiting E3 ubiquitin ligase, and triggers cell cycle arrest and apoptosis. PROTAC BCL6/IKZF1/3 Degrader-1 exhibits favorable anti-tumor activity in diffuse large B-cell lymphoma xenograft models. PROTAC BCL6/IKZF1/3 Degrader-1 can be used for the research of diffuse large B-cell lymphoma.
(Pink: IKZF Family and BCL6 ligand (HY-179064); Blue: Cereblon ligand (HY-41547); Black: linker).
For research use only. We do not sell to patients.
- Formula: C43H49ClN10O7
- Molecular Weight:853.36
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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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Biological Activity
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IKZF1 |
IKZF3 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | DC50 |
0.06 nM
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Degradation of BCL6-eGFP in HEK 293T cells stably expressing BCL6-eGFP assessed by western blot analysis after 3 h incubation.
Degradation of BCL6-eGFP in HEK 293T cells stably expressing BCL6-eGFP assessed by western blot analysis after 3 h incubation.
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41086092 |
| HEK-293T | DC50 |
0.03 nM
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Degradation of BCL6-eGFP in HEK 293T cells stably expressing BCL6-eGFP assessed by western blot analysis after 12 h incubation.
Degradation of BCL6-eGFP in HEK 293T cells stably expressing BCL6-eGFP assessed by western blot analysis after 12 h incubation.
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41086092 |
| OCI-Ly10 | DC50 |
0.64 nM
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Degradation of BCL6 in OCI-ly10 cells assessed by western blot analysis after 24 h incubation.
Degradation of BCL6 in OCI-ly10 cells assessed by western blot analysis after 24 h incubation.
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41086092 |
| OCI-Ly10 | DC50 |
14.74 nM
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Degradation of IKZF1 in OCI-ly10 cells assessed by western blot analysis after 24 h incubation.
Degradation of IKZF1 in OCI-ly10 cells assessed by western blot analysis after 24 h incubation.
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41086092 |
| OCI-Ly10 | DC50 |
1.05 nM
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Degradation of IKZF3 in OCI-ly10 cells assessed by western blot analysis after 24 h incubation.
Degradation of IKZF3 in OCI-ly10 cells assessed by western blot analysis after 24 h incubation.
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41086092 |
| OCI-Ly1 | DC50 |
0.08 nM
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Degradation of BCL6 in OCI-ly1 cells assessed by western blot analysis after 24 h incubation.
Degradation of BCL6 in OCI-ly1 cells assessed by western blot analysis after 24 h incubation.
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41086092 |
| OCI-Ly1 | DC50 |
5.74 nM
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Degradation of IKZF1 in OCI-ly1 cells assessed by western blot analysis after 24 h incubation.
Degradation of IKZF1 in OCI-ly1 cells assessed by western blot analysis after 24 h incubation.
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41086092 |
| OCI-Ly1 | DC50 |
6.31 nM
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Degradation of IKZF3 in OCI-ly1 cells assessed by western blot analysis after 24 h incubation.
Degradation of IKZF3 in OCI-ly1 cells assessed by western blot analysis after 24 h incubation.
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41086092 |
| OCI-Ly1 | IC50 |
0.46 nM
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Antiproliferative activity against OCI-ly1 cells assessed after 7 days incubation.
Antiproliferative activity against OCI-ly1 cells assessed after 7 days incubation.
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41086092 |
| SU-DHL-6 | IC50 |
35.68 nM
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Antiproliferative activity against SU-DHL6 cells assessed after 7 days incubation.
Antiproliferative activity against SU-DHL6 cells assessed after 7 days incubation.
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41086092 |
PROTAC BCL6/IKZF1/3 Degrader-1 (BC6) potently degrades BCL6 in HEK 293T cells stably expressing BCL6-eGFP, with DC50 values of 0.03 nM at 12 and 24 h[1].
PROTAC BCL6/IKZF1/3 Degrader-1 (0.05-100 nM; 0.5-24 h) potently degrades BCL6, IKZF1 and IKZF3 in OCI-ly10 cells in a time- and concentration-dependent manner via the ubiquitin-proteasome pathway[1].
PROTAC BCL6/IKZF1/3 Degrader-1 (0.014-100 nM; 24 h) potently degrades BCL6, IKZF1 and IKZF3 in OCI-ly1 cells[1].
PROTAC BCL6/IKZF1/3 Degrader-1 efficiently degrades BCL6, IKZF1 and IKZF3 in SU-DHL4 cells in a time- and concentration-dependent manner via the ubiquitin-proteasome pathway, with a 24 h DC50 of 1.04 nM for BCL6, 26.32 nM for IKZF1, and 6.40 nM for IKZF3[1].
PROTAC BCL6/IKZF1/3 Degrader-1 (administered for 7 consecutive days) exhibits potent antiproliferative activity against a variety of GCB- and ABC-DLBCL cell lines, with IC50 values ranging from 0.46 to 35.68 nM[1].
PROTAC BCL6/IKZF1/3 Degrader-1 (10 nM; 24 h) activates the interferon pathway and inhibits the cell cycle/mitosis pathway in OCI-ly10 cells, thereby exerting its antiproliferative activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:OCI-ly10 (ABC-DLBCL) cells
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Concentration:0.05, 0.14, 0.41, 1.23, 3.70, 11.1, 33.3, 100 nM (24 h)
50 nM (time-course)
1, 10, 100 nM (IKZF1/3 degradation) -
Incubation Time:24 h (concentration-dependent)
0.5, 1, 2, 3, 6, 12, 24 h (time-dependent)
24 h (IKZF1/3 degradation) -
Result:Induced concentration-dependent degradation of BCL6 (DC50 = 0.64 nM), IKZF1 (DC50 = 14.74 nM), and IKZF3 (DC50 = 1.05 nM) at 24 h.
Caused >70% BCL6 degradation within 1 h in time-dependent analysis, with maximal degradation maintained for 24 h; IKZF1/3 degradation began at 2 h and reached >80% by 24 h.
Blocked degradation of BCL6 via pretreatment with BI-3812, immunomodulatory imide drug, proteasome inhibitor, or NEDD8-activating enzyme inhibitor.
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Cell Line:OCI-ly1 (DLBCL) cells
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Concentration:0.014, 0.04, 0.12, 0.37, 1.1, 3.3, 10, 100 nM
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Incubation Time:24 h
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Result:Induced concentration-dependent degradation of BCL6 (DC50 = 0.08 nM), IKZF1 (DC50 = 5.74 nM), and IKZF3 (DC50 = 6.31 nM) at 24 h.
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Cell Line:SU-DHL4 (GCB-DLBCL) cells
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Concentration:1, 10, 100 nM
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Incubation Time:24 h
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Result:Degraded BCL6, IKZF1, and IKZF3 in SU-DHL4 cells.
| Species | Dose | Route | Tmax | T1/2 | Cmax | AUC0-t | AUC0-∞ | Vd | CL | MRT |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 30 mg/kg | p.o. | 1.67 h | 3.26 h | 373.82 ng/mL | 3359.45 ng/mL·h | 3515.23 ng/mL·h | 36.82 L/kg | 8.64 L/h/kg | 5.46 h |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (female, 6 weeks old, subcutaneous xenograft with 5 × 106 OCI-ly1 cells)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Achieved tumor growth inhibition (TGI) of 63.55% at 25 mg/kg and 72.23% at 50 mg/kg.
Significantly reduced tumor weight compared to the vehicle group at both doses.
Caused no significant changes in body weight over the 21-day period.
Significantly degraded BCL6 and IKZF1/3 in tumor tissues from both dosing groups.
Chemical Information
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Molecular Weight 853.36
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Formula C43H49ClN10O7
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SMILES
CNC(COC1=CC2=C(N(C1=O)C)C=CC(NC3=NC(N4CCC(CC4)CN5CCC(CC5)CCNC6=CC=CC7=C6C(N(C7=O)C8CCC(NC8=O)=O)=O)=NC=C3Cl)=C2)=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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC BCL6/IKZF1/3 Degrader-1 Related Classifications
HY-179075 Related Classifications
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