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AVL-292

Cat. No. M2113
AVL-292 Structure
Synonym:

CC-292

Size Price Availability Quantity
10mg USD 110 In stock
50mg USD 410 In stock
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Quality Control
Biological Activity

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. AVL-292 inhibited osteoclast function and reduced osteoclast-stimulated proliferation of MM cells. 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.

Protocol
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
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 423.44
Formula C22H22FN5O3
CAS Number 1202757-89-8
Purity >99%
Solubility DMSO 60 mg/mL
Storage at -20°C
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
Rating
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
Rating
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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AVL-292, CC-292 supplier, BTK, inhibitors

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