Free shipping on all orders over $ 500

Spebrutinib (AVL-292)

Cat. No. M2113
Spebrutinib (AVL-292) Structure
Synonym:

CC-292; Spebrutinib

Size Price Availability Quantity
5mg USD 58  USD58 In stock
10mg USD 85  USD85 In stock
Free Delivery on orders over USD 500 Bulk Inquiry?

Quality Control & Documentation
Biological Activity

Spebrutinib (AVL-292) is an orally available and highly selective covalent inhibitor of Bruton's tyrosine kinase (Btk) that is currently undergoing Phase 1b clinical development for CLL and B-NHL. AVL-292 selectively and covalently bonds to Btk to inactivate and silence its activity. Spebrutinib (AVL-292) inhibited osteoclast function and reduced osteoclast-stimulated proliferation of MM cells. Spebrutinib (AVL-292) was well tolerated from 125-400 mg po QD and early efficacy analysis in CLL and B-NHL shows 10/11 efficacy evaluable pts with SD. The ongoing phase Ib clinical trial of AVL-292 is being conducted in patients with B-cell malignancies, including B-cell NHL, CLL, and WM.

Customer Product Validations & Biological Datas
Source Allergy (2017). Figure 1. AVL-292
Method flow cytometry
Cell Lines HMC-1 cells, and KU812 cells
Concentrations 0.01-10 μmol/L
Incubation Time 4 hours
Results We found that dasatinib, ibrutinib, AVL-292, and CNX-774 counteract anti-IgE-induced expression of pBTK in BA
Source Allergy (2017). Figure 5. AVL-292
Method proliferation assay
Cell Lines HMC-1 cells and KU812 cells
Concentrations 0.001-10 μmol/L
Incubation Time 48 h
Results As determined by 3H-thymidine uptake, ibrutinib, AVL-292, and P505-15 showed no significant effects on proliferation of HMC-1.1, HMC-1.2, and KU812 cells unless high concentrations (≥1 μmol/L) were applied
Protocol (for reference only)
Cell Experiment
Cell lines naïve human B cells
Preparation method Immunoblot Analysis. Cells were incubated in serum-free RPMI media for 1–1.5 hours. Isolated human B cells were incubated with CC-292 at a final concentration of 0.001, 0.01, 0.1 and 1 μM. Ramos cells were incubated with 0.1 nM–3 μM CC-292. Cells were then incubated in the presence of compound for 1 hour at 37°C. Following incubation, cells were centrifuged and resuspended in 100 μl of serum-free RPMI and BCR was stimulated with addition of 5 μg/ml α-human IgM. Samples were centrifuged, washed in phosphate-buffered saline (PBS), and lysed in 100 μl of Cell Extraction Buffer [cat. no. FNN0011; Life Technologies (Invitrogen), Carlsbad, CA] plus 1:10 (v/v) PhosSTOP Phosphatase Inhibitor (Roche, Basel, Switzerland) and 1:10 (v/v) Complete Protease Inhibitor (cat. no. 11836145001; Roche). Antibodies used for immunoblot analysis include P-PLCγ2 [cat. no. 3872; Cell Signaling Technology, Beverly, MA (CST)], PLCγ2 (3871; CST), Syk (2712; CST), P-Syk (2710; CST), Btk (cat. no. 611116; BD Biosciences, Franklin Lakes, NJ), P-Btk (cat. no. 2207-1; Epitomics, Berlingame, CA), and Tubulin (cat. no. T6199; Sigma-Aldrich, St. Louis, MO). Membranes were scanned on a Li-Cor Odyssey scanner using infrared fluorescence detection (Li-Cor Biosciences, Lincoln, NB)..
Concentrations 0.001, 0.01, 0.1 and 1 μM
Incubation time 1h
Animal Experiment
Animal models Collagen-Induced Arthritis Model
Formulation not mentioned
Dosages 10,30,50 mg/kg
Administration oral
Chemical Information
Molecular Weight 423.44
Formula C22H22FN5O3
CAS Number 1202757-89-8
Solubility (25°C) DMSO 60 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Danilo De Novellis, et al. The TKI Era in Chronic Leukemias

[2] Emanuela Grassilli, et al. p65BTK Is a Novel Biomarker and Therapeutic Target in Solid Tumors

[3] Peter H Schafer, et al. Spebrutinib (CC-292) Affects Markers of B Cell Activation, Chemotaxis, and Osteoclasts in Patients with Rheumatoid Arthritis: Results from a Mechanistic Study

[4] Ali S Abdelhameed, et al. A highly sensitive LC-MS/MS method to determine novel Bruton's tyrosine kinase inhibitor spebrutinib: application to metabolic stability evaluation

[5] Tjeerd Barf, et al. Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile

Related BTK Products
BCPyr

BCPyr is a new candidate BTK degradation agent (DC50 = 800 nM).

BMS-986143

BMS-986143 is a potent, reversible inhibitor of tyrosine kinase (BTK), which has been successfully targeted by a number of irreversible tumor compounds.

BIIB091

The reversible BTK kinase inhibitor BIIB091 is a highly selective phase I clinical candidate compound for multiple sclerosis.

TAK-020

TAK-020 is a highly selective oral covalent BTK inhibitor with a promising safety and tolerability profile for both hematologic malignancies and autoimmune diseases.

BTK inhibitor 1 (Compound 27)

BTK inhibitor 1 (compound 27) is an inhibitor of BTK with an IC50 of 0.11 nM for Btk and inhibits B cell activation in hWB with an IC50 of 2 nM.

  Catalog
Abmole Inhibitor Catalog




Keywords: Spebrutinib (AVL-292), CC-292; Spebrutinib supplier, BTK, inhibitors, activators

Contact Us

Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.