Birelentinib  (Synonyms: DZD8586)

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)^[1][2].

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.

Birelentinib (25 mg/kg; oral; once daily) dose-dependently inhibits tumor growth in an animal model with subcutaneously implanted DLBCL tumor cells^[1].
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 (K_puu,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.

453.44

C₂₃H₂₁F₂N₅O₃

2662512-15-2

NC1=NC=NN2C([C@@H]3CC[C@H](OC3)CO)=NC(C4=CC=C(C=C4)OC5=C(C(F)=CC=C5)F)=C12

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Bai Y, et al. Preclinical Study of DZD8586, a Non-Covalent LYN/BTK Dual Inhibitor with Excellent BBB Penetration, for the Treatment of B-Cell Non-Hodgkin Lymphoma (B-NHL)[J]. Blood, 2023, 142: 2822.

  [2]. Song Y, et al. First report of phase 1 studies of DZD8586, a BBB penetrant LYN/BTK dual inhibitor, in patients with B-cell non-Hodgkin lymphoma (B-NHL)[J]. Blood, 2023, 142: 4465.