Zanubrutinib (BGB-3111)

Catalog No.S8791

Zanubrutinib (BGB-3111) Chemical Structure

Molecular Weight(MW): 471.55

Zanubrutinib (BGB-3111) is a potent, specific and irreversible BTK inhibitor that has been shown to have a lower off-target inhibitory activity on other kinases, including ITK, JAK3 and EGFR.

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Biological Activity

Description Zanubrutinib (BGB-3111) is a potent, specific and irreversible BTK inhibitor that has been shown to have a lower off-target inhibitory activity on other kinases, including ITK, JAK3 and EGFR.
Targets
BTK [1]
(Cell-free assay)
In vitro

In biochemical and cellular assays, BGB-3111 is more selective than ibrutinib for BTK vs. EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, BLK and TEC[1]. In several MCL and DLBCL cell lines, BGB-3111 inhibits BCR aggregation-triggered BTK autophosphorylation, blocks downstream PLC-γ2 signaling, and potently inhibits cell proliferation[2].

In vivo

In preclinical animal studies, BGB-3111 demonstrates superior oral bioavailability, achieving higher exposure and more complete target inhibition in the tissues than ibrutinib[1]. In mouse BTK occupancy assays, treatment with BGB-3111 results in a dose-dependent BTK occupancy and shows about 3-fold more potency than ibrutinib in target organs, including PBMC and spleen[2]. Both in the REC-1 MCL and ABC subtype DLBCL (TMD-8) xenograft models, BGB-3111 induces dose-dependent anti-tumor effects and demonstrates superior efficacy in comparison with ibrutinib. Toxicity study in rats indicates that BGB-3111 is very well tolerated, and the MTD is not reached when it is dosed up to 250 mg/kg/day[3].

Protocol

Solubility (25°C)

In vitro DMSO 94 mg/mL (199.34 mM)
Ethanol 94 mg/mL (199.34 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 471.55
Formula

C27H29N5O3

CAS No. 1691249-45-2
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03561298 Completed Drug: BGB-3111 and Drug Cocktail Healthy Subjects BeiGene June 7 2018 Phase 1
NCT03465059 Completed Drug: Zanubrutinib Hepatic Insufficiency & Healthy Subjects BeiGene May 30 2018 Phase 1
NCT03336333 Active not recruiting Drug: BGB-3111|Drug: Bendamustine|Drug: Rituximab Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma BeiGene November 2 2017 Phase 3
NCT03206918 Active not recruiting Drug: BGB-3111 Relapsed or Refractory Chronic Lymphocytic Leukemia|Relapsed or Refractory Small Lymphocytic Lymphoma BeiGene March 9 2017 Phase 2
NCT03206970 Active not recruiting Drug: BGB-3111 Relapsed or Refractory Mantle Cell Lymphoma BeiGene March 2 2017 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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BTK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID