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Spebrutinib (AVL-292)

Name: Spebrutinib (AVL-292)
Brand: Selleck Chemicals
SKU: S7173
Rating: 5 (11 reviews)

Synonyms: CC-292

Catalog No.S7173 Purity:99.99%

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

CAS No. 1202757-89-8

Purity & Quality Control

Batch: Purity: 99.99%

99.99

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Signaling Pathway

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
Kinase Assay	The Omnia continuous read assay is performed essentially as described by the vendor. The assay conditions are: 40 μM ATP (1X K_MATP), 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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

References

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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.250mg/ml (10.04mM)	Taking the 1 mL working solution as an example, add 50 μL of 85 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.530mg/ml (1.25mM)	Taking the 1 mL working solution as an example, add 50 μL of 10.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

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