Home Angiogenesis BTK inhibitor Spebrutinib (AVL-292) For research use only.

Spebrutinib (AVL-292)

Synonyms: CC-292

Spebrutinib (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 (AVL-292) Chemical Structure

Spebrutinib (AVL-292) Chemical Structure

CAS No. 1202757-89-8

Purity & Quality Control

Spebrutinib (AVL-292) Related Products

Signaling Pathway

BTK Signaling Pathways

BTK Signaling Pathway

Biological Activity

Description Spebrutinib (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
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]
Kinase Assay 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 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.
In Vivo
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]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02031419 Terminated
Lymphoma Large B-Cell Diffuse
Celgene
 December 18 2013 Phase 1
NCT01766583 Completed
Relapsed/Refractory B-cell Lymphoma
The Lymphoma Academic Research Organisation|Celgene Corporation
 February 2013 Phase 1
NCT01351935 Completed
B Cell Non-Hodgkin''s Lymphoma|Chronic Lymphocytic Leukemia|Waldenstrom Macroglobulinemia
Celgene|The Leukemia and Lymphoma Society
 July 18 2011 Phase 1

Chemical Information & Solubility

Molecular Weight 423.44 Formula

C22H22FN5O3
CAS No. 1202757-89-8 SDF Download Spebrutinib (AVL-292) SDF
Smiles COCCOC1=CC=C(C=C1)NC2=NC=C(C(=N2)NC3=CC(=CC=C3)NC(=O)C=C)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 85 mg/mL ( (200.73 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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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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