YL064
YL064 is a multi-target STAT3-c-MYC inhibitor that directly binds to ATXN3 and inhibits its deubiquitinating activity, thereby promoting the ubiquitination and proteasomal degradation of oncogenic substrates of ATXN3. YL064 inhibits the phosphorylation of STAT3-Tyr705 without altering the total protein level of STAT3; meanwhile, it directly binds to the SH2 domain of STAT3 to block the dimerization, nuclear translocation, and DNA-binding activity of STAT3. YL064 directly targets the C-terminal HLH-Zip domain of c-Myc, upregulates the phosphorylation of c-Myc at the Thr58 site, and induces the ubiquitination and proteasome-dependent degradation of c-Myc. YL064 suppresses tumor cell proliferation, induces G2/M cell cycle arrest, reduces cell migration and invasion capacities, and triggers cancer cell apoptosis. YL064 can be used in related research on breast cancer, prostate cancer, diffuse large B-cell lymphoma, and multiple myeloma.
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- CAS 番号: 1240580-64-6
- 分子式: C25H27NO4S
- 分子量:437.55
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保管条件:
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
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
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Stat-3 |
c‑Myc |
ATXN3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
39.71 μM
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Antiproliferative activity against Py8119, MCF-7, and MDA-MB-231 breast cancer cells assessed by CCK-8 assay after 24 h incubation.
Antiproliferative activity against Py8119, MCF-7, and MDA-MB-231 breast cancer cells assessed by CCK-8 assay after 24 h incubation.
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s41419-026-09171-5 |
| PC-3 | IC50 |
44.71 μM
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Antiproliferative activity against PC-3 human prostate cancer cells assessed by CCK-8 assay after 24 h incubation.
Antiproliferative activity against PC-3 human prostate cancer cells assessed by CCK-8 assay after 24 h incubation.
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s41419-026-09171-5 |
体外実験
YL064 (12 μM - gradient concentrations; 15 min) is a potent, concentration-dependent inhibitor of purified recombinant full-length ATXN3 deubiquitinating activity in the cell-free in vitro enzymatic assay[1].
YL064 (100 μM) directly binds to purified full-length recombinant ATXN3 protein in the cell-free thermal shift assay[1].
YL064 (100 μM; 2 h) directly interacts with endogenous ATXN3 in Py8119 mouse breast cancer cells, as confirmed by the cellular thermal shift assay[1].
YL064 exhibits direct physical binding to recombinant full-length ATXN3 protein with a measured KD of 649 μM in the SPR assay[1].
YL064 (24 h) potently inhibits the proliferation of Py8119, MCF-7, and MDA-MB-231 breast cancer cells, with an average IC50 of 39.71 μM following 24 h treatment[1].
YL064 (10-20 μM; 24 h) effectively inhibits STAT3 activation and downstream cyclin D1 and Mcl-1 expression even in U266 human multiple myeloma cells co-cultured with protective HS-5 bone marrow stromal cells[3].
YL064 (10-100 μM; 2 h) directly and selectively binds to STAT3 protein, with competitive displacement confirming specific target interaction[3].
YL064 promotes the post-transcriptional degradation of the ATXN3 substrate KLF4 in Py8119 and MCF-7 breast cancer cells in a dose-dependent manner[1].
YL064 (10 days) significantly suppresses clonogenic survival of MCF-7 and Py8119 breast cancer cells after 10 days of continuous treatment[1].
YL064 (15 μM; overnight incubation, followed by 2 h EdU labeling at 37 °C) suppresses DNA synthesis and cell proliferation in breast cancer cells, as shown by reduced EdU incorporation[1].
YL064 (20 μM; 24 h) potently suppresses both the migratory and invasive capabilities of MCF-7 and MDA-MB-231 breast cancer cells in vitro[1].
YL064 (5-40 μM) reduces YAP protein levels in PC-3 prostate cancer cells in a dose-dependent manner by promoting proteasomal degradation[1].
YL064 (24 h) inhibits the proliferation of PC-3 human prostate cancer cells with an IC50 of 44.71 μM after 24 h of treatment[1].
YL064 (0.1-100 μM; 12-48 h) potently suppresses the viability of OCI-Ly3 and SU-DHL-2 diffuse large B cell lymphoma cells in dose- and time-dependent patterns[2].
YL064 (5-20 μM; 1-12 h) induces dose- and time-dependent reduction of c-Myc protein expression in OCI-Ly3 diffuse large B cell lymphoma cells[2].
YL064 (10 μM; 6 h) triggers proteasome-dependent degradation of c-Myc protein in OCI-Ly3 diffuse large B cell lymphoma cells[2].
YL064 (10 μM; 6 h)-induced c-Myc degradation in OCI-Ly3 diffuse large B cell lymphoma cells occurs independently of the lysosomal degradation pathway[2].
YL064 (25-500 μM) directly interacts with c-Myc protein in OCI-Ly3 diffuse large B cell lymphoma cells, as demonstrated by the dose-dependent reduction in c-Myc thermal stability[2].
YL064 (50 μM; 10×106 excess unlabeled YL064) directly and specifically binds to native c-Myc protein in OCI-Ly3 diffuse large B cell lymphoma cell lysates[2].
YL064 (25-50 μM; 30 min) directly interacts with purified recombinant c-Myc protein in a cell-free in vitro system in a dose-dependent manner[2].
YL064 (Indicated individual concentrations; 48 h) exerts synergistic anti-proliferative effects in combination with ABT-199 in OCI-Ly3 diffuse large B cell lymphoma cells[2].
YL064 (2.5-20 μM; 24 h) selectively inhibits constitutive STAT3 phosphorylation at Tyr705 without affecting Ser727 phosphorylation or total STAT3 protein levels in U266 human multiple myeloma cells[3].
YL064 (20 μM; 0-24 h) causes rapid, near-complete loss of Tyr705 phosphorylated STAT3 within 6 h of treatment in U266 human multiple myeloma cells[3].
YL064 (20 μM; 3-24 h) suppresses expression of the STAT3 downstream pro-survival target proteins cyclin D1 and Mcl-1 in a time-dependent manner in U266 human multiple myeloma cells[3].
YL064 (2.5-20 μM; 6 h) potently blocks IL-6-induced STAT3 Tyr705 phosphorylation in MM1.S human multiple myeloma cells[3].
YL064 (0-100 μM) directly engages STAT3 in intact U266 human multiple myeloma cells, causing dose-dependent thermal destabilization of the target protein[3].
YL064 (20 μM; 24 h) disrupts the dimerization of STAT3 in U266 human multiple myeloma cells[3].
YL064 (2.5-20 μM; 24 h) induces dose-dependent apoptotic cleavage of caspase 3 and PARP-1 in U266 and MM1.S human multiple myeloma cells[3].
YL064 (20 μM; 0-60 min) rapidly suppresses IL-6-induced STAT3 Tyr705 phosphorylation within 1 h of treatment in MM1.S human multiple myeloma cells[3].
YL064 (20 μM; 6 h) blocks IL-6-induced nuclear translocation of STAT3 in MM1.S human multiple myeloma cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:OCI-Ly3 and SU-DHL-2 diffuse large B cell lymphoma cells
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Concentration:0.1-100 μM
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Incubation Time:12 h, 24 h, 48 h
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Result:Reduced the viability of OCI-Ly3 and SU-DHL-2 DLBCL cells in a clear dose-dependent and time-dependent manner.
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Cell Line:OCI-Ly3 diffuse large B cell lymphoma cells
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Concentration:5, 10, 20 μM (12 h incubation); 10 μM (1, 3, 6, 9, 12 h incubation)
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Incubation Time:12 h (5, 10, 20 μM); 1, 3, 6, 9, 12 h (10 μM)
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Result:Markedly reduced c-Myc protein levels in OCI-Ly3 cells in a strict dose-dependent manner when applied for 12 h, and also in a time-dependent manner at the fixed 10 μM concentration. c-Myc protein abundance progressively decreased as YL064 concentration increased, and similarly decreased as treatment duration was extended to 12 h.
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Cell Line:OCI-Ly3 diffuse large B cell lymphoma cells
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Concentration:10 μM
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Incubation Time:6 h
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Result:Strongly reduced c-Myc protein levels in OCI-Ly3 cells.
Co-treatment with proteasome inhibitor blocked this YL064-induced c-Myc degradation, restoring high levels of c-Myc protein in treated cells.\nInduced substantial reduction of c-Myc protein levels.
The lysosome inhibitor did not prevent this YL064-mediated c-Myc degradation, as c-Myc protein levels remained significantly suppressed in the combined treatment group.
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Cell Line:OCI-Ly3 diffuse large B cell lymphoma cells
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Concentration:Indicated individual concentrations of YL064
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Incubation Time:48 h
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Result:Combined with ABT-199 produced a strongly synergistic reduction in OCI-Ly3 cell viability, with greater growth inhibition than either single agent treatment.
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Cell Line:Human multiple myeloma U266 and MM1.S cell lines
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Concentration:2.5, 5, 10, 20 μM
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Incubation Time:24 h
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Result:Induced dose-dependent apoptosis in both U266 and MM1.S cells, with clear appearance of cleaved caspase 3 and cleaved PARP-1 observed starting at 10 μM, and more robust cleavage detected at 20 μM.
Decreased full-length caspase 3 and full-length PARP-1 levels correspondingly with increasing concentration.
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Cell Line:Human U266 multiple myeloma cells
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Concentration:2.5, 5, 10, 20 μM
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Incubation Time:24 h
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Result:Decreased the level of phosphorylated STAT3 (Tyr705) in a dose-dependent manner, with near-complete abrogation of p-STAT3 (Tyr705) observed at 20 μM.
Did not alter levels of phosphorylated STAT3 at Ser727 across all tested concentrations, and left total STAT3 protein levels unchanged.
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Cell Line:Human U266 multiple myeloma cells
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Concentration:20 μM
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Incubation Time:3, 6, 12, 24 h
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Result:Completely abrogated the phosphorylation of STAT3 at Tyr705 as early as 6 h after treatment.
Caused phosphorylation of STAT3 at Ser727 to gradually increase slightly over the 24 h treatment period, and total STAT3 protein levels to decrease progressively with longer incubation time.\nTime-dependently reduced the protein levels of both cyclin D1 and Mcl-1.
Substantially diminished cyclin D1 protein levels after 3 h of treatment, and rendered them almost undetectable by 24 h.
Caused Mcl-1 protein levels to decrease progressively across all tested time points, with clear reduction evident as early as 3 h post-treatment.
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Cell Line:IL-6-stimulated human MM1.S multiple myeloma cells
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Concentration:2.5, 5, 10, 20 μM
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Incubation Time:6 h
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Result:Dose-dependently inhibited IL-6-induced STAT3 phosphorylation at Tyr705.
Produced strong inhibition of p-STAT3 (Tyr705) at 5 μM, and achieved full suppression of IL-6-triggered Tyr705 phosphorylation at 20 μM.
Left total STAT3 protein levels relatively consistent across all treatment groups.
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Cell Line:IL-6-stimulated human MM1.S multiple myeloma cells
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Concentration:20 μM
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Incubation Time:0, 5, 10, 20, 30, 60 min pre-incubation before IL-6 stimulation
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Result:Progressively inhibited the IL-6-induced phosphorylation of STAT3 at Tyr705 with increasing pre-incubation time.
Caused significant reduction in p-STAT3 (Tyr705) after 20 min of pretreatment, and near-complete inhibition of phosphorylation at 60 min post-treatment.
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Cell Line:IL-6-stimulated human MM1.S multiple myeloma cells
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Concentration:20 μM
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Incubation Time:6 h pre-incubation before IL-6 stimulation
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Result:Completely blocked IL-6-triggered nuclear translocation of STAT3, with STAT3 retained in the cytoplasm and no nuclear co-localization with DAPI observed.
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Cell Line:Human U266 multiple myeloma cells, and U266 cells co-cultured with HS-5 human bone marrow stromal cells
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Concentration:10, 20 μM
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Incubation Time:24 h
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Result:Dose-dependently reduced p-STAT3 (Tyr705), cyclin D1, and Mcl-1 levels in monocultured U266 cells, with near-complete loss of all three proteins at 20 μM.
Still reduced p-STAT3 (Tyr705), cyclin D1, and Mcl-1 levels in a dose-dependent manner in U266 cells co-cultured with HS-5 stromal cells, with substantial suppression observed at 20 μM.
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Cell Line:Human U266 multiple myeloma cells
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Concentration:20 μM FITC-YL064
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Incubation Time:8 h
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Result:Generated strong green fluorescent signal from FITC-YL064 that extensively overlapped with the red STAT3 immunofluorescence signal across the cytoplasm of U266 cells, producing a merged orange/yellow fluorescent signal that demonstrated clear intracellular colocalization of YL064 and STAT3.
体内実験
YL064 (30 mg/kg; i.p.; daily; 9 days) significantly suppresses human multiple myeloma xenograft tumor growth in mice with minimal impact on body weight, concomitant with STAT3 pathway inhibition and induction of tumor cell apoptosis[3].
YL064 (30 mg/kg) exerts in vivo anti-lymphoma efficacy in OCI-Ly3 DEL xenograft mice via c-Myc downregulation, reduced tumor cell proliferation, and enhanced tumor cell apoptosis[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J mice (around 6 to 8 weeks old)[1]
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Dosage:20 mg/kg
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Administration:i.p.; alternate days; 6 treatments
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Result:Exerted significant in vivo anti-tumor effects in an orthotopic murine breast cancer model, reducing tumor growth, KLF4 protein levels, and tumor cell proliferation.
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Animal Model:BALB/c nu/nu nude mice (Female, aged 4-6 weeks)[3]
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Dosage:30 mg/kg
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Administration:i.p.; daily; 9 days
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Result:Reduced the tumor burden of MM1.S tumor-bearing mice.
Did not produce notable changes in the body weight of mice.
Decreased expression of proliferating cell nuclear antigen (PCNA) in tumor tissues.
Reduced levels of phosphorylated STAT3 (Tyr705) in tumor tissues.
Suppressed expression of the downstream STAT3 target gene product cyclin D1 in tumor tissues.
Altered TUNEL staining indicative of increased apoptotic cell death within the tumor.
化学情報
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CAS 番号 1240580-64-6
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分子量 437.55
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分子式 C25H27NO4S
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SMILES
CC(C=C1)=CC=C1S[C@@H]2C(C=CC(O)=C3O)=C3[C@@]4(CC(C(OC)=C5)=O)[C@]5([H])[C@@H]2N(CC4)C
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
YL064 関連分類
HY-189126 関連分類
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Keywords
- YL064
- 1240580-64-6
- YL 064
- YL-064
- STAT
- c-Myc
- Small Interfering RNA (siRNA)
- Apoptosis
- ATXN3
- MDA-MB-231 breast cancer cells
- c-MYC
- STAT3
- MCF-7 breast cancer cells
- PC-3 prostate cancer cells
- Py8119 mouse breast cancer cells
- U266 human multiple myeloma cells
- OCI-Ly3 diffuse large B cell lymphoma cells
- MM1.S human multiple myeloma cells
- Inhibitor
- inhibitor
- inhibit