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Spebrutinib (AVL-292) BTK inhibitor

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

Cat.No.S7173

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. It is in Phase 1.

Chemical Structure

Molecular Weight: 423.44

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src FLT3 HER2 Bcr-Abl HIF ALK Syk FAK VDA
Related Products	tirabrutinib(ONO-4059) hydrochloride CGI1746 LFM-A13 CNX-774 BMS-935177 Fenebrutinib (GDC-0853) Branebrutinib (BMS-986195) Evobrutinib BMS-986142 Nemtabrutinib (ARQ 531) Pirtobrutinib (LOXO-305) RN486 BTK inhibitor 1 (Compound 27) NX-2127 ONO-4059 analogue M7583 NX-5948 Poseltinib BGB-8035 Edralbrutinib Atuzabrutinib MT-802 JNJ-64264681 BIIB129 Btk Antibody [M4L24] BTK IN-1 Tolebrutinib PCI 29732 Orelabrutinib Catadegbrutinib (BGB-16673)

Chemical Information, Storage & Stability

Molecular Weight	423.44	Formula	C₂₂H₂₂FN₅O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1202757-89-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	CC-292			Smiles	COCCOC1=CC=C(C=C1)NC2=NC=C(C(=N2)NC3=CC(=CC=C3)NC(=O)C=C)F

Solubility

In vitro
Batch:

DMSO : 85 mg/mL (200.73 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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.

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.

Mechanism of Action

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/IC₅₀/Ki	BTK ^[1] (Cell-free assay) <0.5 nM
In vitro	Spebrutinib (AVL-292) exhibits dose-dependent inhibition of Btk with EC50 of 8 nM and downstream BCR signaling components in Ramos cells. ^[1] By inhibiting BTK activities, it 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 of Spebrutinib (AVL-292), 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.
In vivo	In a collagen-induced arthritis mouse model, Spebrutinib (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]
References	[1] http://www.celgene.com/pdfs/2011_ASH_AVL-292.pdf [2] https://pubmed.ncbi.nlm.nih.gov/23709115/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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