ZS34
ZS34 is a potent, orally active, and selective MAT2A inhibitor with an IC50 of 13.7 nM, displaying minimal hERG and UGT1A1 liabilities. ZS34 selectively suppresses the growth of methylthioadenosine phosphorylase (MTAP)-deficient cancer cells by inhibiting SAM synthesis, reducing SDMA levels, and inducing DNA damage. ZS34 exhibits antitumor efficacy in a HCT116 MTAP-/- xenograft mouse model. ZS34 can be used for the research of MTAP-deficient cancer.
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- CAS No.: 3106086-17-0
- Formule: C18H14ClN3O2
- Masse moléculaire:339.78
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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
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MAT2A 13.7 nM (IC50) |
ZS34 (10 days) inhibits the proliferation of MTAP deficiency cells (NCI-H838, NCI-H1437, MCF-7, MDA-MB-231 and MIA PaCa-2 cells) with IC50s of 1.70, 386, 38.1, 37.2, and 115 nM, respectively, exhibiting selectivity over MTAP proficiency cells (A-375, AsPC-1, DU145, NCI-H460 and NCI-H520) with IC50s >10000 nM[1].
ZS34 (10 days) exhibits potent antiproliferative effects against HCT116 MTAP-null cells (IC50 = 124 nM) but weak activity against WT HCT116 cells (IC50 > 10000 nM), demonstrating excellent selectivity inhibition with a selective indices (SI) exceeding 80.6[1].
ZS34 (0-10 μM; 96 h) selectively induces DNA damage in MTAP-deficient HCT116 cells through MAT2A inhibition[1].
ZS34 binds to the allosteric site of the MAT2A dimer, forming hydrogen bonds with Arg313 and a coordinated water molecule, and engaging in π-π stacking with Phe20, Trp274, and Phe18, while its ortho-methyl group participates in a CH-π interaction with Phe333[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116 (MTAP-/-) and HCT116 (WT)
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Concentration:0, 0.1, 1 μM
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Incubation Time:96 h
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Result:Induced a dose-dependent decrease in the SDMA level, in HCT116 MTAP-/- cells, but not in HCT116 WT cells.
Induced a marked increase in γH2AX levels, a marker of DNA damage, in HCT116 MTAP-/- cells, but not in HCT116 WT cells.
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Cell Line:HCT116 (MTAP-/-) and HCT116 (WT)
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Concentration:0.1, 1, 10 μM
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Incubation Time:96 h
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Result:led to a marked increase in γH2AX levels in HCT116 MTAP-/-cells compared to the control, but not in HCT116 WT cells.
ZS34 (400 mg/kg, p.o., single dose) shows no obvious toxicity in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female ALB/c nude mice subcutaneously inoculated with HCT116 MTAP-/- cells[1]
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Dosage:10, 30 mg/kg
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Administration:p.o., daily for 30 days
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Result:Significantly suppressed tumor growth, with tumor growth inhibition (TGI) values of 57.3% and 89.0% at 10 and 30 mg/kg, respectively.
Showed a tendency to cause tumor regression at 30 mg/kg.
Reduced SAM levels in tumors.
Showed no significant body weight loss compared to control.
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Animal Model:ICR mice[1]
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Dosage:400 mg/kg
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Administration:p.o., single dose
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Result:Was well tolerated at this high dose.
Chemical Information
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CAS No. 3106086-17-0
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Masse moléculaire 339.78
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Formule C18H14ClN3O2
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SMILES
O=C1N(C2=C(C(NC)=N1)C3=C(C(Cl)=C2)C=CO3)C4=CC=CC=C4C
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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)
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