ZSL-M028
ZSL-M028 is an orally active and selective Polo-like kinase 4 (PLK4) inhibitor with an IC50 value of 1.1 nM. ZSL-M028 exhibits anti-tumor activity against TRIM37-amplified neuroblastoma, downregulates SAS6, upregulates FBXW5, induces G2-phase cell cycle arrest and apoptosis, activates the p53 signaling pathway, and inhibits tumor cell colony formation and migration. ZSL-M028 shows significant tumor growth inhibitory activity in the IMR-32 neuroblastoma xenograft model. ZSL-M028 can be used in neuroblastoma-related research.
For research use only. We do not sell to patients.
- Formula: C27H29FN5O2P
- Molecular Weight:505.52
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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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Help & FAQs
Biological Activity
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PLK4 1.1 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| IMR-32 | IC50 |
0.289 μM
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Antiproliferative activity against TRIM37-amplified IMR-32 neuroblastoma cells assessed via cell proliferation inhibition assay.
Antiproliferative activity against TRIM37-amplified IMR-32 neuroblastoma cells assessed via cell proliferation inhibition assay.
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42463132 |
| MCF7 | IC50 |
0.518 μM
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Antiproliferative activity against TRIM37-amplified MCF-7 breast cancer cells assessed via cell proliferation inhibition assay.
Antiproliferative activity against TRIM37-amplified MCF-7 breast cancer cells assessed via cell proliferation inhibition assay.
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42463132 |
| NCI-H460 | IC50 |
3.234 μM
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Antiproliferative activity against non-amplified NCI-H460 lung cancer cells assessed via cell proliferation inhibition assay.
Antiproliferative activity against non-amplified NCI-H460 lung cancer cells assessed via cell proliferation inhibition assay.
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42463132 |
ZSL-M028 (compound B33) selectively inhibits the proliferation of TRIM37-amplified IMR-32 and MCF-7 cells, with IC50 values of 0.289 μM and 0.518 μM, respectively, while showing weak activity against non-amplified NCI-H460 cells (IC50 = 3.234 μM)[1].
ZSL-M028 (0.1-1.0 μM; 14 days) inhibits colony formation of TRIM37-amplified MCF-7 cells in a concentration-dependent manner[1].
ZSL-M028 (0.25-1.0 μM; 24 h) significantly inhibits the migration of TRIM37-amplified MCF-7 cells[1].
ZSL-M028 (1-8 μM; 48 h) regulates the PLK4 signaling pathway, upregulates FBXW5 levels and downregulates SAS6 levels in TRIM37-amplified cancer cells[1].
ZSL-M028 (0.1-1.0 μM; 48 h) induces apoptosis in IMR-32 cells in a concentration-dependent manner and arrests the cell cycle at the G2 phase[1].
ZSL-M028 exhibits favorable metabolic stability in human liver microsomes with a half-life of 667.0 min, while showing species-dependent stability in rat and mouse liver microsomes; it also displays a moderate plasma protein binding rate[1].
ZSL-M028 is a selective PLK4 inhibitor that potently inhibits purified PLK4 kinase with an IC50 of 1.1 nM; it shows weak inhibitory activity against Aurora A (IC50 = 1.847 μM), with a selectivity of over 1600-fold[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 breast cancer cells
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Concentration:0.1, 0.25, 0.5, 1 μM
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Incubation Time:14 days
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Result:Inhibited colony formation of TRIM37-amplified MCF-7 cells in a concentration-dependent manner.
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Cell Line:MCF-7 breast cancer cells
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Concentration:0.25, 0.5, 1 μM
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Incubation Time:24 h
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Result:Suppressed MCF-7 cell migration in a time- and concentration-dependent manner.
Reduced wound recovery observed at all tested concentrations after 24 h.
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Cell Line:MCF-7 breast cancer cells
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Concentration:1, 2, 4, 8 μM
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Incubation Time:48 h
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Result:Modulated the PLK4 signaling pathway, increasing FBXW5 levels and decreasing SAS6 levels.
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Cell Line:IMR-32 cell
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Concentration:0.1, 0.25, 0.5, 1.0 μM
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Incubation Time:48 h
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Result:Triggered concentration-dependent apoptosis in IMR-32 cells: 63.6% apoptotic cells at 0.5 μM and 92.3% at 1.0 μM, stronger than positive control LCR-263 (HY-18682).
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Cell Line:IMR-32 cell
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Concentration:0.1, 0.25, 0.5, 1.0 μM
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Incubation Time:48 h
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Result:Blocked IMR-32 cell cycle at G2 phase concentration-dependently.
| Species | Dose | Route | T1/2 | AUC0-t | CL | Vdss | F |
|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 0.6 h | 448 ng·h/mL | 36.8 mL/min/kg | 1.5 L/kg | / |
| Mice[1] | 10 mg/kg | p.o. | 1.5 h | 2480 ng·h/mL | / | / | 55.4 % |
| Rat[1] | 1 mg/kg | i.v. | 0.5 h | 664 ng·h/mL | 25.1 mL/min/kg | 1.1 % | / |
| Rat[1] | 10 mg/kg | p.o. | 1.5 h | 656 ng·h/mL | / | / | 10.1 % |
| Rat[1] | 30 mg/kg | p.o. | 1.6 h | 644 ng·h/mL | / | / | 32.3 % |
ZSL-M028 (200 mg/kg, single oral gavage; 7 days) does not cause persistent body weight loss in ICR mice. Only male mice show slight platelet reduction, and all hematological indicators remain within the physiological normal range; no visible toxic damage occurs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c‑nu mice (6‑8 weeks old) were subcutaneously injected with IMR‑32 cells (1 × 107 cells per mouse in 200 μL cold PBS mixed with equal‑volume Matrigel)[1]
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Dosage:30 mg/kg
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Administration:Oral gavage; twice daily; for 24 days
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Result:Demonstrated prominent antitumor efficacy (TGI = 68.38%) without obvious body weight loss.
Chemical Information
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Molecular Weight 505.52
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Formula C27H29FN5O2P
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SMILES
CP(C(C=CC(F)=C1)=C1CNC2=CC3=NC(NC4=CC=C(C=C4)N5CCOCC5)=NC=C3C=C2)(C)=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)
ZSL-M028 Related Classifications
HY-187506 Related Classifications
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