GS-9973
(Synonyms: GS-9973) 目录号 : GC16430
A selective spleen tyrosine kinase inhibitor
Cas No.:1229208-44-9
Sample solution is provided at 25 µL, 10mM.
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GS-9973 is a selective inhibitor of Syk with IC50 value of 7.7 nM [1].
Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase that is expressed mainly in hematopoietic cells and acts as a mediator of immunoreceptor signaling. Syk can be used for therapy of autoimmune, oncology indications and allergy [1].
GS-9973 is an orally bioavailable and selective Syk inhibitor. GS-9973 showed good absorption potential and high bioavailability. In monocytes, GS-9973 inhibited immune-complex-stimulated cytokine production and BCR-mediated proliferation and activation of B-cells [1]. In chronic lymphocytic leukemia (CLL) cells, GS-9973 significantly reduced pAkt and ribosomal S6 phosphorylation. These results suggested that GS-9973 inhibited B-cell receptor (BCR) mediated signaling pathways. In CLL samples, the combination of GS-9973 and idelalisib synergistically reduced CLL cell viability [2].
In chronic lymphocytic leukemia patients, GS-9973 inhibited adenopathy and reduced lymph node [3].
References:
[1]. Currie KS, Kropf JE, Lee T, et al. Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase. J Med Chem, 2014, 57(9): 3856-3873.
[2]. Burke RT1, Meadows S, Loriaux MM, et al. A potential therapeutic strategy for chronic lymphocytic leukemia by combining Idelalisib and GS-9973, a novel spleen tyrosine kinase (Syk) inhibitor. Oncotarget, 2014, 5(4): 908-915.
[3]. Sharman J, Hawkins M, Kolibaba K, et al. An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia. Blood, 2015, 125(15): 2336-2343.
| Kinase experiment [1]: | |
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Kinase assays |
Full-length baculovirus-expressed Syk kinase activity was measured in a Lance-based assay format in a final volume of 25 μL containing 25 mM Tris-HCl, pH 7.5, 5 mM β-glycerophosphate, 2 mM DTT, 0.1 mM Na3VO4, 10 mM MgCl2, 0.5 μM Promega PTK biotinylated peptide substrate 1, 0.01% casein, 0.01% Triton X-100, 0.25% glycerol, and 40 mM ATP (Km for ATP) incubated at room temperature for 60 mins. Reactions were stopped with the addition of 30 mM EDTA containing 30 μL of SA-APC and 4 nM PT-66 antibody and the plates were measured on a Perkin-Elmer Envision. IC50 values for test compounds were determined using a four-parameter linear regression algorithm. |
| Cell experiment [1]: | |
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Cell lines |
MV-4-11 cells |
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Preparation method |
The solubility of this compound in DMSO is > 20.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
10 μM; 72 hrs |
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Applications |
GS-9973 selectively inhibited Syk in cells, and potently suppressed BCR-mediated activation and proliferation of B-cells as well as immune-complex-induced cytokine production in monocytes. |
| Animal experiment [1]: | |
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Animal models |
Rat collagen-induced arthritis (CIA) model |
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Dosage form |
1 ~ 10 mg/kg; p.o.; b.i.d. |
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Applications |
In a rat CIA model, GS-9973 (1 ~ 10 mg/kg; p.o.; b.i.d.) significantly reduced ankle inflammation. Moreover, GS-9973 also showed disease-modifying activity in several histological measurements, including inhibition of pannus formation, cartilage damage, bone resorption, as well as periosteal bone formation with the ED50 values ranging from 1.2 to 3.9 mg/kg. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Currie KS, Kropf JE, Lee T, et al. Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase. J Med Chem, 2014, 57(9): 3856-3873. |
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| Cas No. | 1229208-44-9 | SDF | |
| 别名 | GS-9973 | ||
| 化学名 | 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine | ||
| Canonical SMILES | C12=NC=CN1C=C(C3=CC=C(C=NN4)C4=C3)N=C2NC5=CC=C(N6CCOCC6)C=C5 | ||
| 分子式 | C23H21N7O | 分子量 | 411.46 |
| 溶解度 | ≥ 20.55mg/mL in DMSO | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4304 mL | 12.1518 mL | 24.3037 mL |
| 5 mM | 0.4861 mL | 2.4304 mL | 4.8607 mL |
| 10 mM | 0.243 mL | 1.2152 mL | 2.4304 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet