Spebrutinib (AVL-292)

製品コードS7173 バッチS717301

印刷

化学情報

Chemical Structure Synonyms CC-292 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H22FN5O3
分子量 423.44 CAS No. 1202757-89-8
Solubility (25°C)* 体外 DMSO 85 mg/mL (200.73 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Spebrutinib (AVL-292) is a covalent, orally active, and highly selective BTK inhibitor with IC50 of <0.5 nM, displaying at least 1400-fold selectivity over the other kinases assayed. Phase 1.
in vitro AVL-292 exhibits dose-dependent inhibition of Btk with EC50 of 8 nM and downstream BCR signaling components in Ramos cells. [1] AVL-292, by inhibiting BTK activities, further inhibits B cell proliferation with EC50 of 3 nM. [2]
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. [2]
特徴 Orally bioavailable BTK-selective inhibitor that has been tested in Phase I clinical trials for treatment of relapsed or refractory B-NHL, CLL and WM.

プロトコル(参考用のみ)

キナーゼアッセイ Procedures for BTK OMNIA 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 mMβ-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.
細胞アッセイ 細胞株 Human B cells
濃度 ~1000 nM
反応時間 72 hours
実験の流れ 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.
動物実験 動物モデル Collagen-induced arthritis mouse model
投薬量 ~30 mg/kg
投与方法 Oral administration

カスタマーフィードバック

, , Allergy, 2017, 72(11):1666-1676

, , J Biomol Screen, 2015, 20(7):876-886.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells [ Elife, 2021, 10e66984] PubMed: 34704555
Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function [ Am J Physiol Cell Physiol, 2021, 320(5):C902-C915] PubMed: 33689480
Combining ibrutinib and checkpoint blockade improves CD8+ T-cell function and control of chronic lymphocytic leukemia in Em-TCL1 mice. [ Haematologica, 2020, 10.3324/haematol.2019.238154] PubMed: 32139435
Differential impact of BTK active site inhibitors on the conformational state of full-length BTK [ Elife, 2020, 9e60470] PubMed: 33226337
Differential impact of BTK active site inhibitors on the conformational state of full-length BTK [ Elife, 2020, 9e60470] PubMed: 33226337
Effects of Inhibitors against Syk-BTK-PI3K Signaling on Platelet Function [ ScholarsArchive@OSU, 2020, None] PubMed: None
Effects of Inhibitors against Syk-BTK-PI3K Signaling on Platelet Function [ ScholarsArchive@OSU, 2020, 51] PubMed: N/A
Inhibition of Bruton's Tyrosine Kinase Modulates Microglial Phagocytosis: Therapeutic Implications for Alzheimer's Disease [ J Neuroimmune Pharmacol, 2019, 10.1007/s11481-019-09839-0] PubMed: 30758770
Improving CLL Vγ9Vδ2-T-cell fitness for cellular therapy by ex vivo activation and ibrutinib [ Blood, 2018, 132(21):2260-2272] PubMed: 30213872
BTK inhibition is a potent approach to block IgE-mediated histamine release in human basophils. [Smiljkovic D, et al. Allergy, 2017, 10.1111/all.13166] PubMed: 28328081

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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