product name CC-292 (AVL-292)
Description: CC-292, also known as AVL-292 or CC-292, is a potent, covalent, orally bioactive, and highly selective BTK inhibitor with IC50 of <0.5 nM, displaying at least 1400-fold selectivity over the other kinases assayed. CC-292 targets and covalently binds to BTK, thereby preventing its activity. By irreversibly inhibiting BTK, administration of this agent may lead to an inhibition of B cell receptor (BCR) signaling and may inhibit cell proliferation of B-cell malignancies.
References: J Pharmacol Exp Ther. 2013 Aug;346(2):219-28; Br J Haematol. 2013 Nov;163(4):436-43.
423.44
Formula
C22H22FN5O3
CAS No.
1202757-89-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 85 mg/mL (200.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
CC-292,LMK-435
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401355
| In Vitro |
In vitro activity: AVL-292 exhibits dose-dependent inhibition of Btk with EC50 of 8 nM and downstream BCR signaling components in Ramos cells. AVL-292, by inhibiting BTK activities, further inhibits B cell proliferation with EC50 of 3 nM. Kinase Assay: The Omnia continuous read assay is performed essentially as described by the vendor. The assay conditions are: 40 μM ATP (1X KMATP), 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 mMβ-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 Assay: 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 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. |
| Animal model | Collagen-induced arthritis (CIA) mouse model |
| Formulation & Dosage | 3-30 mg/kg; p.o |
| References | J Pharmacol Exp Ther. 2013 Aug;346(2):219-28; Br J Haematol. 2013 Nov;163(4):436-43. |
Related Posts
product name CC-292 (AVL-292)
Description: CC-292, also known as AVL-292 or CC-292, is a potent, covalent, orally bioactive, and highly selective BTK inhibitor with IC50 of <0.5 nM, displaying at least 1400-fold selectivity over the other kinases assayed. CC-292 targets and covalently binds to BTK, thereby preventing its activity. By irreversibly inhibiting BTK, administration of this agent may lead to an inhibition of B cell receptor (BCR) signaling and may inhibit cell proliferation of B-cell malignancies.
References: J Pharmacol Exp Ther. 2013 Aug;346(2):219-28; Br J Haematol. 2013 Nov;163(4):436-43.
423.44
Formula
C22H22FN5O3
CAS No.
1202757-89-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 85 mg/mL (200.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
CC-292,LMK-435
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401355
| In Vitro |
In vitro activity: AVL-292 exhibits dose-dependent inhibition of Btk with EC50 of 8 nM and downstream BCR signaling components in Ramos cells. AVL-292, by inhibiting BTK activities, further inhibits B cell proliferation with EC50 of 3 nM. Kinase Assay: The Omnia continuous read assay is performed essentially as described by the vendor. The assay conditions are: 40 μM ATP (1X KMATP), 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 mMβ-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 Assay: 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 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. |
| Animal model | Collagen-induced arthritis (CIA) mouse model |
| Formulation & Dosage | 3-30 mg/kg; p.o |
| References | J Pharmacol Exp Ther. 2013 Aug;346(2):219-28; Br J Haematol. 2013 Nov;163(4):436-43. |