All AbMole products are for research use only, cannot be used for human consumption.
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.
 |
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 |
| 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 |
| 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 |
[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
| Related BTK Products |
|---|
| UBX-382
UBX-382 is an orally available proteolysis-targeting chimeras (PROTACs) that target BTK to inactivate B-cell receptor signaling. |
| GDC-0834
GDC-0834 is a potent and selective BTK inhibitor. |
| DD-03-171
DD-03-171 is a BTK, IKFZ1 and IKFZ3 degrader, the BTK IC50 a value of 5.1 nM. |
| N-piperidine Ibrutinib hydrochloride
N-piperidine Ibrutinib hydrochloride is a reversible Ibrutinib derivative. |
| (R)-NX-2127
(R)-NX-2127 (compound 28) is a first-in-class, orally bioavailable Bruton’s Tyrosine Kinase (Btk) degrader. (R)-NX-2127 mediates the degradation of transcription factors IKZF1 and IKZF3 through molecular glue interactions with the cereblon E3 ubiquitin ligase complex. NX-2127 degrades common BTK resistance mutants, including BTKC481S. |
All AbMole products are for research use only, cannot be used for human consumption or veterinary use. We do not provide products or services to individuals. Please comply with the intended use and do not use AbMole products for any other purpose.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2024 AbMole BioScience. All Rights Reserved.
