Zanubrutinib

SKU: orb1299685

Description

Zanubrutinib (BGB-3111) is a potent and selective small molecule Bruton's tyrosine kinase (BTK) inhibitor. It is widely used in biochemical and cellular research to investigate B-cell receptor signaling and has demonstrated efficacy in preclinical in vivo models of B-cell malignancies.

Research Area

Cardiovascular Research, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 1691249-45-2
• MW: 471.55
• Purity: 98.42% (May vary between batches)
• Formula: C₂₇H₂₉N₅O₃
• SMILES: NC(=O)c1c2NCC[C@@H](C3CCN(CC3)C(=O)C=C)n2nc1-c1ccc(Oc2ccccc2)cc1
• Target: BTK
• Solubility: DMSO:257.5 mg/mL (546.07 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (10.6 mM)

Bioactivity

• Target IC50:
  Jurkat cells:3477 nM|Rec1 cells:0.36 nM|HEK293 cells:204.7 nM|OCI-LY1 cells:0.35 nM|Sf9 cells:0.3 nM|TMD8 cells:3.8 nM|MOLM-13 cells:5095 nM|BTK:0.3 nM|Ramos cells:1.8 nM
• In Vivo:
  In mouse BTK occupancy assays, treatment with zanubrutinib resulted in a dose-dependent BTK occupancy and showed about 3-fold more potency than ibrutinib in target organs, including PBMC and spleen.zanubrutinib induced dose-dependent anti-tumor effects against REC-1 MCL xenografts engrafted either subcutaneously or systemically via tail vein injection in mice.In the subcutaneous xenografts, zanubrutinib at 2.5 mg/kg BID showed similar activity as ibrutinib at 50 mg/kg QD, its clinical relevant dose.In the systemic model, the median survival of zanubrutinib 25 mg/kg BID group was significantly longer than those of both ibrutinib 50 mg/kg QD and BID groups.In an ABC-subtype DLBCL (TMD-8) subcutaneous xenograft model, zanubrutinib also demonstrated better anti-tumor activity than ibrutinib.Preliminary 14-day toxicity study in rats showed that zanubrutinib was very well tolerated and maximal tolerate dose (MTD) was not reached when it was dosed up to 250mg/kg/day.
• In Vitro:
  In both biochemical and cellular assays, zanubrutinib demonstrated nanomolar BTK inhibition activity. In several MCL and DLBCL cell lines, zanubrutinib inhibited BCR aggregation-triggered BTK autophosphorylation, blocked downstream PLC-γ2 signaling, and potently inhibited cell proliferation. In comparison with ibrutinib, zanubrutinib showed much more restricted off-target activities against a panel of kinases, including ITK. While ibrutinib significantly inhibited rituximab-induced NK cell IFN-γ secretion and in vitro cytotoxicity on mantle cell lymphoma cells, zanubrutinib was at least 10-fold weaker than ibrutinib in inhibiting rituximab induced ADCC, consistent with its weak ITK inhibition activity.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, Bruton tyrosine kinase, BGB 3111, BGB3111, BGB-3111, Btk, BTK, zanubrutinib

Compound Identifiers

PubChem CID

135565884