规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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体外研究 (In Vitro) |
体外活性:Bafetinib 阻断 WT Bcr-Abl 自磷酸化及其下游激酶活性,在 K562 和 293T 细胞中的 IC50 分别为 11 nM 和 22 nM。 Bafetinib 可有效抑制 Bcr-Abl 阳性细胞系(包括 K562、KU812 和 BaF3/wt 细胞)的生长,而不影响 Bcr-Abl 阴性 U937 细胞系的增殖。此外,Bafetinib 对 Bcr-Abl 点突变细胞系(例如 BaF3/E255K 细胞)表现出剂量依赖性抗增殖作用。在 Bcr-Abl+ 白血病细胞系中,Bafetinib 通过阻断 Bcr-Abl 的磷酸化来诱导 caspase 介导的和不依赖 caspase 的细胞死亡。激酶测定:使用 SignaTECT 蛋白酪氨酸激酶测定,在含有 250 μM 肽底物、740 Bq/μL [γ-33P]ATP 和 20 μM 冷三磷酸腺苷 (ATP) 的 25 μL 反应混合物中进行 Bcr-Abl 激酶测定系统。每种 Bcr-Abl 激酶的使用浓度为 10 nM。使用酶联免疫吸附测定 (ELISA) 试剂盒对 Abl、Src 和 Lyn 进行激酶测定。使用 KinaseProfiler 测试 NS-187 对 79 种酪氨酸激酶的抑制作用。细胞测定:K562、BaF3/wt、BaF3/E255K 和 BaF3/T315I 细胞以 1 × 103 铺板于 96 孔板中,而 KU812 和 U937 细胞以 5 × 103 铺板于 96 孔板中。将细胞与连续稀释的 Bafetinib 一起孵育 3 天。通过 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑;Nacalai Tesque)测定法测量细胞增殖,并通过将数据拟合来计算 50% 抑制浓度 (IC50) 值逻辑曲线。
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体内研究 (In Vivo) |
在 Bcr-Abl 阳性 KU812 小鼠模型中,巴非替尼 (0.2 mg/kg/天) 显着抑制肿瘤生长,并且在 20 mg/kg/天时完全抑制肿瘤生长,且没有副作用。对于 Balb/c 小鼠,Bafetinib 的最大耐受剂量为 200 mg/kg/d,生物利用度 (BA) 为 32%。在含有 Ba/F3/wt bcr-ablGFP、Ba/F3/Q252H 或 Ba/F3/M351T 细胞的中枢神经系统 (CNS) 白血病模型中,巴非替尼 (60 mg/kg) 和环孢菌素 A (CsA) 联合治疗(50 mg/kg) 比单独使用 Bafetinib 或 CsA 更能显着抑制大脑中的白血病生长。
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动物实验 |
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参考文献 |
分子式 |
C30H31F3N8O
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分子量 |
576.62
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CAS号 |
859212-16-1
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相关CAS号 |
859212-16-1;887650-05-7;
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SMILES |
O=C(NC1=CC=C(C)C(NC2=NC=CC(C3=CN=CN=C3)=N2)=C1)C4=CC=C(CN5C[C@@H](N(C)C)CC5)C(C(F)(F)F)=C4
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InChi Key |
ZGBAJMQHJDFTQJ-DEOSSOPVSA-N
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InChi Code |
InChI=1S/C30H31F3N8O/c1-19-4-7-23(13-27(19)39-29-36-10-8-26(38-29)22-14-34-18-35-15-22)37-28(42)20-5-6-21(25(12-20)30(31,32)33)16-41-11-9-24(17-41)40(2)3/h4-8,10,12-15,18,24H,9,11,16-17H2,1-3H3,(H,37,42)(H,36,38,39)/t24-/m0/s1
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化学名 |
(S)-N-(3-([4,5'-bipyrimidin]-2-ylamino)-4-methylphenyl)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)benzamide
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别名 |
INNO-406; INNO 406; NS187; NS187; INNO406;NS-187; NS 187
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
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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溶解度 (体外) |
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溶解度 (体内) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (4.34 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中,混匀;然后向上述溶液中加入50 μL Tween-80,混匀;加入450 μL生理盐水定容至1 mL。 *生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 配方 2 中的溶解度: ≥ 2.5 mg/mL (4.34 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。 例如,若需制备1 mL的工作液,可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。 View More
配方 3 中的溶解度: 0.5% methylcellulose+0.2% Tween 80: 30 mg/mL 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7342 mL | 8.6712 mL | 17.3424 mL | |
5 mM | 0.3468 mL | 1.7342 mL | 3.4685 mL | |
10 mM | 0.1734 mL | 0.8671 mL | 1.7342 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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 ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT01215799 | Completed | Drug: Bafetinib | Hormone Refractory Prostate Cancer | CytRx | August 2010 | Phase 2 |
NCT01144260 | Completed | Drug: bafetinib | B-Cell Chronic Lymphocytic Leukemia | CytRx | June 2010 | Phase 2 |
NCT01234740 | Completed | Drug: bafetinib Procedure: microdialysis |
Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma |
City of Hope Medical Center | December 2010 | Phase 1 |
NCT00352677 | Completed | Drug: INNO-406 | Chronic Myeloid Leukemia Acute Lymphocytic Leukemia |
CytRx | July 2006 | Phase 1 |
The tyrosine kinase inhibitor bafetinib blocks PAR2-TRPV4 coupling. (A) Bafetinib (1–10 μM) concentration dependently inhibited the sustained [Ca2+]i response to SLIGRL (30 μM), without affecting the peak response to SLIGRL or GSK1016790A (GSK, 30 nM). (B) Analysis showing concentration-dependent inhibition of the SLIGRL-induced coupling response with bafetinib in the TRPV4-transfected HEK293 cells. (C) 10 μM bafetinib inhibited the sustained [Ca2+]i response to trypsin, but did not affect the peak response to trypsin or the response to GSK1016790A. (D) 10 μM bafetinib inhibited trypsin-induced coupling in TRPV4 HEK cells compared with vehicle-treated (Veh) controls. Data are presented as mean ± SEM of n = 6–7 experiments.*P < 0.05, significantly different from NT HEK control. #P < 0.05, significantly different from vehicle-treated TRPV4 HEK control. td> |
Bafetinib inhibits the expression of PD-L1 in vivo. (A) Tumor image of Balb/c mice treated with or without Bafetinib (30 mg/kg daily). (B) Tumor volume of Balb/c mice treated with or without Bafetinib (30 mg/kg daily). (C) The body weights of Balb/c mice were measured every other day. (D) Expression of PD-L1 in tumors of Balb/c mice. The relative protein level of PD-L1 in CT26 was quantitatively analyzed below. (E) Tumor volume of immunodeficient nude mice treated with or without Bafetinib (30 mg/kg daily). (F) The body weights of immunodeficient nude mice. (G) Expression of PD-L1 in tumors of immunodeficient nude mice. The relative protein level of PD-L1 in CT26 was quantitatively analyzed below. Bars, mean ± SEM (n = 6). *, p < 0.05. n. s: not significant. (H) H292 cells were treated with control Bafetinib (2.5 μM) or anti-PD-L1. T cells were isolated from peripheral blood and stimulated via anti-CD3/CD28/CD2. Co-incubation was carried out with these treated H292 cells for 8–12 h (T cells: Tumor cells = 5:1). After incubation, surviving cells were then fixed and stained with crystal violet. Sacle bar: 300 μm. td> |
Bafetinib inhibits the expression of PD-L1 in lung cancer. (A) Screening on H292 cells treated with different small molecule drugs (10 μM) for 24 h. (B) The expression of PD-L1 protein was measured by Western blot in H292 cells, which were treated with Bafetinib (0.625, 1.25, and 2.5 μM) for 24 h. The relative protein level of PD-L1 in H292 was quantitatively analyzed on the right. (C) Expression of B7-H3, Galectin-9, PD-L1, and CD47 was measured by Western blot in H292 cells when treated with Bafetinib (2.5 μM) for 24 h (D, E) The expression of PD-L1 protein was measured by Western blot in H460, H358, PC9 cells, and primary lung cancer when treated with Bafetinib (0.625, 1.25, and 2.5 μM) for 24 h. (F) Surface PD-L1 expression on H292 treated with Bafetinib (0.625, 1.25, and 2.5 μM) was determined by flow cytometry. Cells were estimated for PD-L1 or mouse IgG control antibodies. Data were the mean ± SEM of quadruplicate experiments. The data were analyzed by one-way ANOVA with Dunnett’s post hoc test. ***, p < 0.001; *, p < 0.05. td> |