Birelentinib
Birelentinib (DZD8586) is an orally effective, selective, non-covalent inhibitor targeting LYN tyrosine kinase and BTK tyrosine kinase, capable of penetrating the blood-brain barrier. Birelentinib exhibits concentration-dependent antiproliferative effects in RI-1 cells and diffuse large B-cell lymphoma (DLBCL) cell lines carrying BTK resistance mutations (such as C481X, V416L, etc.). Birelentinib blocks both BTK-dependent and independent signaling of the B-cell receptor (BCR), thereby inhibiting tumor cell proliferation and inducing cell death. Birelentinib can be used in research to overcome resistance to existing covalent and non-covalent BTK inhibitors in B-cell non-Hodgkin lymphoma (B-NHL).
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- CAS No.: 2662512-15-2
- Formule: C23H21F2N5O3
- Masse moléculaire:453.44
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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
- Pureté et documentation
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Activité biologique
Description
In Vitro
In Western blot experiments using FARAGE cells (DLBCL), birelentinib blocked both BTK-dependent and independent signaling pathways, significantly downregulating the phosphorylation levels of p-BTK (Y223, Y551) and p-LYN[1].
Birelentinib, assessed by pBTK enzyme-linked immunosorbent assay (ELISA), showed a good correlation between its plasma concentration and the regulation of pBTK in whole blood and tumor tissue, demonstrating clear pharmacodynamic characteristics[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Birelentinib (50 mg/kg, 100 mg/kg; oral; once daily) significantly inhibits tumor growth and induces tumor regression in an animal model with intracranially implanted DLBCL tumor cells (TMD-8-Luci), demonstrating good anti-central nervous system lymphoma activity in the intracranial model, and showing a good correlation between plasma concentration and pBTK regulation in whole blood and tumor tissue[1].
Birelentinib (50 mg/kg, 100 mg/kg; oral; once daily) shows superior antitumor activity compared to Tirabrutinib 100 mg/kg in a brain tumor animal model with intracranially implanted TMD-8-Luci cells[1].
The unbound concentration ratio of Birelentinib (DZD8586) in cerebrospinal fluid to plasma (Kpuu,CSF) is 1.2 and 1.3 in rats and monkeys, respectively.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Subcutaneous tumor model induced by diffuse large B-cell lymphoma (DLBCL) cell lines[1]
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Dosage:25 mg/kg, 50 mg/kg, 100 mg/kg
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Administration:Administered orally once daily (qd)
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Result:Exerted profound dose-dependent tumor growth inhibition. At doses of 50 mg/kg and above, it induced tumor regression compared with the vehicle control group. There was a good correlation between the plasma concentration of Birelentinib and the modulation of pBTK in whole blood and tumor tissue.
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Animal Model:Intracranial tumor model induced by DLBCL TMD-8-Luci cells[1]
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Dosage:25 mg/kg, 50 mg/kg, 100 mg/kg
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Administration:Administered orally once daily (qd); control group: Tirabrutinib 100 mg/kg qd (oral)
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Result:Demonstrated significant anti-tumor efficacy in the intracranial DLBCL model, with dose-dependent inhibition of tumor growth.
Induced tumor regression at doses of 50 mg/kg and above.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2662512-15-2
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Masse moléculaire 453.44
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Formule C23H21F2N5O3
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SMILES
NC1=NC=NN2C([C@@H]3CC[C@H](OC3)CO)=NC(C4=CC=C(C=C4)OC5=C(C(F)=CC=C5)F)=C12
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Synonyms
DZD8586
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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)
Birelentinib Related Classifications
HY-160167 Related Classifications
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