Home Angiogenesis BTK inhibitor Spebrutinib (CC-292)

Spebrutinib (CC-292)

Catalog No.S7173 Synonyms: AVL-292

For research use only.

Spebrutinib (CC-292, AVL-292) is a covalent, orally active, and highly selective BTK inhibitor with IC50 of <0.5 nM, displaying at least 1400-fold selectivity over the other kinases assayed. Phase 1.

Spebrutinib (CC-292) Chemical Structure

CAS No. 1202757-89-8

Selleck's Spebrutinib (CC-292) has been cited by 11 Publications

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Biological Activity

Description Spebrutinib (CC-292, AVL-292) is a covalent, orally active, and highly selective BTK inhibitor with IC50 of <0.5 nM, displaying at least 1400-fold selectivity over the other kinases assayed. Phase 1.
Features Orally bioavailable BTK-selective inhibitor that has been tested in Phase I clinical trials for treatment of relapsed or refractory B-NHL, CLL and WM.
Targets
BTK [1]
(Cell-free assay)
<0.5 nM
In vitro

AVL-292 exhibits dose-dependent inhibition of Btk with EC50 of 8 nM and downstream BCR signaling components in Ramos cells. [1] AVL-292, by inhibiting BTK activities, further inhibits B cell proliferation with EC50 of 3 nM. [2]
In vivo In a collagen-induced arthritis mouse model, AVL-292 (3- 30 mg/kg, p.o.) dose-dependently inhibits the clinical signs of inflammatory disease, including reduction in joint and paw swelling and visible redness of the affected paws. [2]

Protocol (from reference)

Kinase Assay:[2]
  • Procedures for BTK OMNIA Assay:

    The Omnia continuous read assay is performed essentially as described by the vendor. The assay conditions are: 40 μM ATP (1X KMATP), 10 μM Y5-Sox, and 10 nM BTK enzyme. Briefly, a substrate mix containing 1.13X ATP and the Y5 Sox substrate is first prepared in 1X Omnia Kinase Reaction Buffer (KRB) consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mMβ-glycerophosphate, 5% glycerol, and 0.2 mM DTT. For IC50 measurements, 5 μL of enzyme are incubated with serially diluted (3-fold) compounds prepared in 50% DMSO in a Corning (#3574) 384-well, white, non-binding surface microtiter plate at 25°C for 30 min. Kinase reactions are started with the addition of 45 μL of the ATP/Y5 substrate mix and monitored at λex360/λem485 in a Synergy 4 plate reader for 60 minutes. Progress curves from each well are examined for linear reaction kinetics and fit statistics. Initial velocity from each reaction is determined from the slope of a plot of relative fluorescence units versus time and then plotted against inhibitor concentration to estimate IC50 using the Response, Variable Slope model in GraphPad Prism from GraphPad Software.

Cell Research:[2]
  • Cell lines: Human B cells
  • Concentrations: ~1000 nM
  • Incubation Time: 72 hours
  • Method: A suspension of resting purified naïve human B cells isolated by negative selection in RPMI is prepared at 0.4–0.5 × 106 cells/ml. Cells are mixed together with α-human IgM (final concentration of 5 μg/ml in each well) and vehicle (dimethyl sulfoxide) or AVL-292 (final concentrations of 0.01, 0.1, 1.0, 10.0, 100.0, or 1000 nM per well) and seeded in a 96-well plate. Cells are incubated for 56 hours in a humidified incubator maintained at 37°C and 5% CO2. 3H-Thymidine is added (final concentration of 1 μCi in each well) and cells are incubated overnight, harvested, and measured for 3H incorporation. Experiments are performed in triplicate.

Solubility (25°C)

In vitro

 DMSO 85 mg/mL
(200.73 mM)
Water Insoluble
Ethanol Insoluble

Chemical Information

Molecular Weight 423.44
Formula

C22H22FN5O3
CAS No. 1202757-89-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COCCOC1=CC=C(C=C1)NC2=NC=C(C(=N2)NC3=CC(=CC=C3)NC(=O)C=C)F

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02031419 Active not recruiting Drug: CC-122|Drug: CC-223|Drug: Rituximab|Drug: CC-292 Lymphoma Large B-Cell Diffuse Celgene December 18 2013 Phase 1
NCT01766583 Completed Drug: CC-292 + lenalidomide Relapsed/Refractory B-cell Lymphoma The Lymphoma Academic Research Organisation|Celgene Corporation February 2013 Phase 1
NCT01351935 Completed Drug: AVL-292 B Cell Non-Hodgkin''s Lymphoma|Chronic Lymphocytic Leukemia|Waldenstrom Macroglobulinemia Celgene|The Leukemia and Lymphoma Society July 18 2011 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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.

Handling Instructions

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