HZ-A-018
HZ-A-018 is an orally active BTK inhibitor (IC50 = 4.0 nM) that inhibits BTK phosphorylation and AKT/S6 ribosomal protein phosphorylation by binding to cysteine 481 in the ATP-binding site, induces apoptosis, and decreases RRM2 expression, sensitizing gastric cancer cells to 5-Fluorouracil (5-FU) (HY-90006). HZ-A-018 can be used for research on gastric cancer and relapsed or refractory B-cell malignancies.
For research use only. We do not sell to patients.
- CAS No.: 2379884-70-3
- Formula: C27H24N6O2
- Molecular Weight:464.52
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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
Description
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Akt |
BTK 4.0 nM (IC50) |
In Vitro
HZ-A-018 (10-40 µM; 72 h) exhibits antiproliferative activity in HGC-27 and BGC-823 gastric cancer cells and shows stronger cytotoxicity than Acalabrutinib (ACP-196) (HY-17600)[1].
HZ-A-018 (72 h, followed by 8 days) inhibits colony formation of HGC-27 and BGC-823 gastric cancer cells[1].
HZ-A-018 (24 h) inhibits the AKT/S6 signaling pathway in HGC-27 and BGC-823 gastric cancer cells, and this inhibitory effect is enhanced when combined with 5-FU[1].
ACP-196 (24 h) exhibits moderate inhibition of the AKT/S6 pathway in BGC-823 gastric cancer cells, but not in HGC-27 gastric cancer cells[1].
HZ-A-018 (10 µM; 72 h) in combination with 5-Fluorouracil (5-FU) (HY-90006) synergistically induces apoptosis in HGC-27 and BGC-823 gastric cancer cells[1].
HZ-A-018 (72 h) in combination with 5-FU induces apoptosis in HGC-27 and BGC-823 gastric cancer cells, as evidenced by the cleavage of PARP and caspase-3[1].
HZ-A-018 (48 h) alone does not alter RRM2 expression, but the combination of HZ-A-018 and 5-FU reduces RRM2 protein expression in HGC-27 and BGC-823 cells[1].
HZ-A-018 (10 μM; 48 h) induces apoptosis in gastric cancer cells by promoting PARP and Caspase-3 cleavage, downregulating Mcl-1, and upregulating Bim[1].
HZ-A-018 (10 μM; 8 h) inhibits BTK phosphorylation at Tyr233 in HGC-27 gastric cancer cells[1].
HZ-A-018 is a highly selective covalent BTK inhibitor with an IC50 of 4.0 nM for BTK kinase inhibition in purified kinase assays[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HGC-27 and BGC-823
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Concentration:10, 20, 30, 40 µM
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Incubation Time:72 h
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Result:Displayed dose-dependent inhibitory effects with much greater cytotoxicity than ACP-196.
Determined IC50 values for HGC-27 and BGC-823 cells.
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Cell Line:HGC-27 and BGC-823
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Concentration:10 µM (in combination with 5-FU)
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Incubation Time:72 h
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Result:Resulted in a substantial increase in apoptotic cells compared with mono-treatment.
Reached an apoptosis rate up to 40% after 72 h treatment.
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Cell Line:gastric cancer cells
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Concentration:40 µM (CHX); 5 µM (MG-132)
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Incubation Time:0, 4, 8, 16, 24 h (CHX); 4, 8, 16 h (MG-132)
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Result:Pretreatment with MG-132, but not cycloheximide, attenuated the inhibitory effects of the combined treatment on RRM2 protein levels.
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Cell Line:HGC-27
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Concentration:10 μM
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Incubation Time:8 h
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Result:Reduced the levels of phosphorylated BTK at Tyr233 compared to untreated controls.
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Cell Line:HGC-27 and BGC-823
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Concentration:10 μM
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Incubation Time:48 h
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Result:Resulted in the cleavage of PARP and Caspase-3, as indicated by increased levels of cl-PARP and cl-Caspase-3.
Decreased the levels of the anti-apoptotic protein Mcl-1.
Increased the levels of the pro-apoptotic protein Bim.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (female, 4 weeks old, HGC-27 xenograft model)[1]
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Dosage:100 mg/kg
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Administration:p.o.; once a day
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Result:Partially prevented tumor growth with a tumor weight of 0.61 g.
Achieved a significantly smaller tumor size than single treatment when combined with 5-FU.
Did not alter the expression of RRM2.
Chemical Information
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CAS No. 2379884-70-3
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Molecular Weight 464.52
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Formula C27H24N6O2
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SMILES
CC#CC(N1CCC[C@H]1C2=NC(C3=CC=C(C=C3)C(NC4=CC=CC=C4)=O)=C5C(N)=NC=CN25)=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)
HZ-A-018 Related Classifications
HY-187675 Related Classifications
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