WK500B
WK500B is a potent and orally active BCL6 inhibitor with a KD of 1.61 μM. WK500B engages intracellular BCL6 and disrupts BCL6‑corepressor interactions to reactivate BCL6 target genes. WK500B exerts cytotoxicity against diffuse large B‑cell lymphoma cells and induces apoptosis and cell cycle arrest. WK500B suppresses germinal center formation in C57BL/6 mice and DLBCL tumor growth in SCID xenograft models without observable toxicity. WK500B can be used for the study of diffuse large B‑cell lymphoma (DLBCL).
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- No. CAS: 2253985-29-2
- Fòrmula: C22H23BrFN7O
- Peso molecular:500.38
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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CXCR4 |
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Cell Line
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Type | Value | Description | References |
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| DOHH-2 | IC50 |
1100 nM
Compound: 13; WK500B
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Antitumor activity against BCL6 dependent human DOHH-2 cells assessed as cell growth inhibition
Antitumor activity against BCL6 dependent human DOHH-2 cells assessed as cell growth inhibition
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[PMID: 36441945] |
| Farage | IC50 |
1100 nM
Compound: 13; WK500B
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Antitumor activity against BCL6 dependent human Farage cells assessed as cell growth inhibition
Antitumor activity against BCL6 dependent human Farage cells assessed as cell growth inhibition
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[PMID: 36441945] |
| L02 | IC50 |
21.61 μM
Compound: 13; WK500B
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Antitumor activity against human L02 cells assessed as cell growth inhibition
Antitumor activity against human L02 cells assessed as cell growth inhibition
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[PMID: 36441945] |
| OCI-Ly7 | IC50 |
1100 nM
Compound: 13; WK500B
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Antitumor activity against BCL6 dependent human OCILY7 cells assessed as cell growth inhibition
Antitumor activity against BCL6 dependent human OCILY7 cells assessed as cell growth inhibition
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[PMID: 36441945] |
| SUD4 | IC50 |
1.39 μM
Compound: 13; WK500B
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Antitumor activity against BCL6 dependent human SU-DHL-4 cells assessed as cell growth inhibition
Antitumor activity against BCL6 dependent human SU-DHL-4 cells assessed as cell growth inhibition
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[PMID: 36441945] |
| SU-DHL-6 | IC50 |
1100 nM
Compound: 13; WK500B
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Antitumor activity against BCL6 dependent human SU-DHL-6 cells assessed as cell growth inhibition
Antitumor activity against BCL6 dependent human SU-DHL-6 cells assessed as cell growth inhibition
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[PMID: 36441945] |
WK500B (2.5-10 μM; 24 h) dose-dependently and specifically inhibits BCL6 BTB domain-mediated transcriptional repression in 293T cells, with near-complete inhibition at 10 μM[1].
WK500B (2.5-10 μM; 24 h) can reactivate BCL6 target genes (p53, CDKN1A, CXCR4, CD69) in BCL6-dependent SUDHL4 and Farage DLBCL cells in a dose-dependent and specific manner, but has no such effect in Toledo cells that do not express BCL6[1].
WK500B directly binds to the purified BCL6 BTB protein with a KD of 1.61 μM and inhibits the interaction between purified BCL6 BTB protein and SMRT peptide with an IC50 of 1.37 μM[1].
WK500B (24 h) disrupts the colocalization of BCL6 and its corepressor SMRT in SUDHL4 DLBCL cells[1].
WK500B (2.5-10 μM; 24 h) can induce dose-dependent S-phase cell cycle arrest in SUDHL4 diffuse large B-cell lymphoma (DLBCL) cells, with 78% of cells in S phase at a concentration of 10 μM; it can also induce dose-dependent apoptosis, with an apoptosis rate of 66.0% at 10 μM[1].
WK500B (1.25-10 μM; 72 h) selectively inhibits proliferation of BCL6-dependent DLBCL cell lines (SUDHL4, SUDHL6, OCI-Ly7, Farage, DOHH2) with sub- to low-micromolar IC50 values, has minimal effects on normal cell lines, and its antiproliferative activity is dependent on BCL6 expression[1].
WK500B (2 μM; 24 h for single agent, 72 h for combinations) synergizes with PRMT5 inhibitor GSK591 (HY-100235) and EZH2 inhibitor GSK343 (HY-13500) to enhance BCL6 target gene reactivation and antiproliferative activity in SUDHL4 DLBCL cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SUDHL4 DLBCL cells, Farage DLBCL cells, Toledo BCL6-null cells
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Concentration:2.5, 5, 10 μM
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Incubation Time:24 h
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Result:Dose-dependently reactivated expression of p53, CDKN1A, CXCR4, and CD69 at 10 μM in SUDHL4 cells and Farage cells.
Had no effect on expression of these genes at 10 μM in Toledo BCL6-null cells.
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Cell Line:DLBCL cell lines (SUDHL4, SUDHL6, OCI-Ly7, Farage, DOHH2), normal cell lines (NCM460, PNT1A, LO2, HAF), SUDHL4 cells transfected with BCL6 shRNA or scramble shRNA
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Concentration:1.25, 2.5, 5, 10 μM
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Incubation Time:72 h
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Result:Inhibited proliferation of DLBCL cell lines with IC50 values of 1.93 μM (SUDHL4), 1.10 μM (SUDHL6), 2.16 μM (OCI-Ly7), 1.19 μM (Farage), and 1.52 μM (DOHH2).
Had much weaker effects on normal cell lines, with IC50 values of 13.99 μM (NCM460), 12.61 μM (PNT1A), 21.61 μM (LO2), and 11.02 μM (HAF).
Showed little inhibitory effect across 1.25-10 μM in SUDHL4 cells with BCL6 knockdown, while dose-dependently inhibiting proliferation of scramble shRNA-transfected control cells.
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Cell Line:SUDHL4 DLBCL cells
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Concentration:2.5, 5, 10 μM
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Incubation Time:24 h
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Result:Induced dose-dependent cell cycle arrest at the S phase: 57% S phase at 2.5 μM, 63% S phase at 5 μM, and 78% S phase at 10 μM.
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Cell Line:SUDHL4 DLBCL cells
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Concentration:2.5, 5, 10 μM
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Incubation Time:24 h
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Result:Induced dose-dependent apoptosis: total apoptotic cells (Annexin V-positive) were 4.81% at 2.5 μM, 25.43% at 5 μM, and 66.0% at 10 μM.
WK500B (12.5-25 mg/kg; p.o.; daily; 18 days) potently suppresses DLBCL tumour growth in SCID mice, reactivates BCL6 target genes, reduces tumour cell proliferation, and shows no detectable toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (8-week-old male, immunized intraperitoneally with NP-CGG)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 12 days
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Result:Reduced the frequency of germinal center B cells (GL7+FAS+B220+) to 0.4%.
Caused a profound loss of germinal centers detected by immunofluorescent staining.
Reduced the proportion of follicular helper T cells (CXCR5+PD1+CD4+).
Decreased titres of high-affinity NP-specific IgG1 (NP5-BSA) and total NP-specific IgG1 (NP23-BSA) in serum.
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Animal Model:SCID (6-8-week-old male, injected subcutaneously with 1×107 SUDHL4 cells)[1]
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Dosage:12.5 mg/kg; 25 mg/kg
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Administration:p.o.; daily; 18 days
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Result:Significantly suppressed tumour growth compared to controls, with reduced tumour weights and volumes.
Reactivated BCL6 target genes (p53, CDKN1A, CXCR4, CD69) in tumour tissue.
Significantly decreased Ki67-positive proliferating tumour cells.
Caused no significant changes in mouse body weight, and no obvious organ damage was detected via histology.
Chemical Information
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No. CAS 2253985-29-2
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Peso molecular 500.38
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Fòrmula C22H23BrFN7O
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SMILES
N(C1=NC(=NC=C1F)N2C[C@H](C)N[C@H](C)C2)C3=CC=C(NC(=O)C=4N=C(Br)C=CC4)C=C3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
WK500B Related Classifications
HY-148640 Related Classifications
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