TSL2109
TSL2109 is an orally active and selective DYRK2 and CDK4/6 inhibitor with an IC50 value of 22 nM for DYRK2. TSL2109 exhibits high kinase selectivity over 93%. TSL2109 arrests cell cycle and induces apoptosis in virto. TSL2109 effectively overcomes Enzalutamide (HY-70002) resistance by suppressing tumor growth in vivo and virto. TSL2109 also shows CDK4/6 inhibitor resistance.TSL2109 demonstrates safety profile. TSL2109 can be used for prostate cancer research and breast cancer[1][2].
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- CAS No.: 2619847-12-8
- Formule: C28H33FN8OS
- Masse moléculaire:548.68
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
Description
In Vitro
TSL2109 (0.5-2 μM,72 h-5 days) exhibits potent antiproliferative activity (IC50 = 0.933 μM) and dose-dependent cell growth inhibitory activity in PCa DU145 cells and exerts significant inhibitory effects proliferation, induces significant G1 phase cell cycle arrest, and promotes apoptosis in 22Rv1 cell [1].
TSL2109 (0.5-2 μM, 24 h) arrests cell cycle at G1 phase and promotes apoptosis in DU145 cells[1].
TSL2109 significantly inhibits the E2F targets and G2M checkpoint pathways in DU145 cells and 22Rv1 cells , upregulates the apoptosis and P53 pathways in DU145 cells[1].
TSL2109 (0.001-1000 μM, 7 days) demonstrates superior growth inhibition in Enzalutamide-resistant in PCa organoids (PDOs) (PR6513B) [1].
TSL2109 significantly suppresses proliferation in androgen receptor (AR) inhibitor-resistant PCa cells and organoids[2].
TSL2109 downregulates p-RB, p-4E-BP1 and BCL2[2].
TSL2109 markedly suppresses the E2F and G2M signaling pathways[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:PCa DU145 cells
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Concentration:0.5, 1, 2 μM
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Incubation Time:5 days
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Result:Shows a dose-dependent cell growth inhibitory activity.
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Cell Line:DU145 and 22Rv1 cell cells
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Concentration:0.5, 1, 2 μM
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Incubation Time:24 h
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Result:Arrested cell cycle at G1 phase in a concentration-dependent manner.
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Cell Line:DU145 and 22Rv1 cells
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Concentration:0.5, 1, 2 μM
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Incubation Time:24 h
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Result:Promoted apoptosis in a concentration-dependent manner.
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Cell Line:22Rv1 and DU145 cell
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Concentration:0.5, 1, 2 μM
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Incubation Time:72 h
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Result:Exerted significant inhibitory effects on 22Rv1 cell proliferation.
In Vivo
TSL2109 (1000 mg/kg, o.p, once) has excellent tolerability and no adverse behavioral effects with safety profile in DU145 mice xenografts[1].
TSL2109 (75 mg/kg, o.p, once daily for 21 days) demonstrates the potential in overcoming Enzalutamide resistance and shows promise in enhancing the efficacy of enzalutamide[1].
TSL2109 (100 mg/kg, once a day for 30 days) demonstrates the potential in overcoming Enzalutamide in in Enzalutamide-resistant PDX mice models[1].
TSL2109 effectively inhibits tumor growth of AR inhibitor-resistant PDX models[2].
TSL2109 shows a potent efficacy in CDK4/6 inhibitor-resistant breast cancer models[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:DU145 cell induced-Male BALB/c nude mice[1]
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Dosage:1000 mg/kg
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Administration:o.p, once
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Result:Exhibited normal body weight gain.
Caused no adverse behavioral effects during a 48 h observation period.
Maintained normal weight gain over 14 days.
Observed no significant changes in the weights of major organs (heart, liver, spleen, lung, kidney) after 14 days.
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Animal Model:DU145 cell induced-Male BALB/c nude mice[1]
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Dosage:100 and 200 mg/kg
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Administration:o.p, once daily for 15 days
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Result:Obviously inhibited 22Rv1 xenografts tumor growth.
Improved tumor growth inhibitory activity when combination with Enzalutamide.
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Animal Model:PDX tissue (s.c.) induced-male NU/ NU mice[1]
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Dosage:100 mg/kg
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Administration:once a day for 30 days
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Result:Induced robust tumor growth suppression.
Significantly reduced tumor burden.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Patient-Derived Orthotopic Xenograft (PDOX)
- Protocol for Cell Cycle
- Subcutaneous Cell-Line-Derived Xenograft
- Breast Cancer Modeling
- Orthotopic Cell-Line Xenograft
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2619847-12-8
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Masse moléculaire 548.68
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Formule C28H33FN8OS
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SMILES
FC1=C(C2=CC=C3N=C(SC3=C2)N(CC)CC)N=C(NC4=NC=C(C=C4)C(N5CCN(CC5)C(C)C)=O)N=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TSL2109 Related Classifications
HY-180574 Related Classifications
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