| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Spebrutinib (formerly known as AVL-292 and CC-292) is a novel, potent, covalent/irreversible, orally bioactive, and highly selective Btk kinase inhibitor with an IC50 of 0.5 nM. By covalently attaching itself to BTK, spebrutinib inhibits its function. Spebrutinib may inhibit B-cell malignancy cell proliferation by blocking BTK irreversibly, which may also result in an inhibition of B cell receptor (BCR) signaling.
| Targets |
Btk (IC50 < 0.5 nM)
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|---|---|
| ln Vitro |
Spebrutinib (CC-292) is a covalent, highly selective, orally active inhibitor of Btk with IC50 value of 0.5 nM. Spebrutinib also has IC50s of 723 nM, 1.729 μM, 2.43 μM, 4.4 μM, and 7.15 μM for Yes, c-Src, Brk, Lyn, and Fyn, respectively, indicating less potent inhibition of these genes. Following a thorough investigation, it was discovered that the cellular EC50 of Btk kinase inhibition with Spebrutinib (EC50=8 nM) and the EC50 of Btk occupancy from a Spebrutinib dose-response in Ramos cells (EC50=6 nM) correlate. Moreover, it has been observed that the concentration of Spebrutinib needed to achieve 90% occupancy of Btk is 39 nM, whereas the concentration at which it inhibits 90% of Btk activity in Ramos cells is 35 nM[1].
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| Cell Assay |
In RPMI media free of serum, cells are cultured for one to one and a half hours. At final concentrations of 0.001, 0.01, 0.1, and 1 μM, isolated human B cells are cultured with spebrutinib. A solution of 0.1 nM–3 μM spebrutinib is added to Ramos cells. Subsequently, the cells are incubated for an hour at 37°C with the compound present. Once the cells have been incubated, they are centrifuged and resuspended in 100 μL of serum-free RPMI. Next, 5 μg/mL of α-human IgM is added to stimulate the BCR. The specimens undergo centrifugation, followed by a PBS wash and lysing in 100 μL of Cell Extraction Buffer supplemented with 1:10 (v/v) PhosSTOP Phosphatase Inhibitor and 1:10 (v/v) Complete Protease Inhibitor. The following antibodies are used in immunoblot analysis: Btk, P-Btk, Tubulin, Syk (2712; CST), P-PLCγ2, PLCγ2 (3871; CST), and Syk (2712; CST). Infrared fluorescence detection is used on a Li-Cor Odyssey scanner to scan membranes[1].
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| References |
| Molecular Formula |
C28H28FN5O6S
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|---|---|
| Molecular Weight |
581.615228652954
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| Exact Mass |
476.32635992
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| CAS # |
1360053-81-1
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| Related CAS # |
Spebrutinib;1202757-89-8
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| Appearance |
Solid
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| SMILES |
COCCOC1=CC=C(C=C1)NC2=NC=C(C(=N2)NC3=CC(=CC=C3)NC(=O)C=C)F.C1=CC=C(C=C1)S(=O)(=O)O
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| InChi Key |
ABSXPNGWJFAPRT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H22FN5O3.C6H6O3S/c1-3-20(29)25-16-5-4-6-17(13-16)26-21-19(23)14-24-22(28-21)27-15-7-9-18(10-8-15)31-12-11-30-2;7-10(8,9)6-4-2-1-3-5-6/h3-10,13-14H,1,11-12H2,2H3,(H,25,29)(H2,24,26,27,28);1-5H,(H,7,8,9)
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| Chemical Name |
benzenesulfonic acid;N-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide
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| Synonyms |
AVL292; AVL-292; AVL 292; CC292; CC-292; CC 292
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 45 mg/mL (~106.3 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7193 mL | 8.5967 mL | 17.1934 mL | |
| 5 mM | 0.3439 mL | 1.7193 mL | 3.4387 mL | |
| 10 mM | 0.1719 mL | 0.8597 mL | 1.7193 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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