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TP-0903

度博替尼
Catalog No.
B5940
AXL受体酪氨酸激酶抑制剂,抗癌药
组合的产品项目
规格价格库存 数量
5mg
¥ 727.00
现货
10mg
¥ 1,090.00
现货
50mg
¥ 4,090.00
现货
100mg
¥ 5,909.00
现货

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A

背景

TP-0903对AXL的IC50值为0.027 μM.

AXL和其它TAM家族成员在维持癌细胞的间充质表型中起着重要作用.间充质细胞增强侵袭与迁移特性,在应激环境下提高细胞存活率,以及增加对靶向治疗的耐受性.TP-0903是一种有效的抗癌药,靶向作用于AXL受体酪氨酸激酶.

体外:基于TP-0903在生化实验中显示出的效力,在基于细胞的实验中对TP-0903活性进行评价.胰腺癌细胞系PSN-1的细胞活力实验表明,TP-0903具有高度有效的活性.此外,在胰腺癌细胞中评估TP-0903阻断GAS6介导的AXL激活的能力.在各种浓度的TP-0903存在时,PSN-1细胞经血清饥饿后用GAS6刺激[1].

体内:在癌症的细胞模型与临床前动物模型中,TP-0903逆转间充质表型驱动的耐受性,从而恢复对Erlotinib的敏感性[2].

临床试验:截至目前,TP-0903仍处于临床前开发阶段.

参考文献:
[1] Mollard A, Warner SL, Call LT, Wade ML, Bearss JJ, Verma A, Sharma S, Vankayalapati H, Bearss DJ.  Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Med Chem Lett. 2011 Dec 8;2(12):907-912.
[2] ToleroPharmaceuticals, Inc–TP-0903.  http://www.toleropharmaceuticals.com/TP-0903.html.

文献引用

化学属性

Physical AppearanceA solid
StorageStore at -20°C
M.Wt516.06
Cas No.1341200-45-0
FormulaC24H30ClN7O2S
Solubility≥25.8 mg/mL in DMSO with gentle warming; insoluble in EtOH; insoluble in H2O
Chemical Name2-((5-chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide
SDFDownload SDF
Canonical SMILESCN(S(C1=CC=CC=C1NC2=NC(NC3=CC=C(CN4CCN(CC4)C)C=C3)=NC=C2Cl)(=O)=O)C
运输条件 蓝冰运输或根据您的需求运输。
一般建议不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。

试验操作

Cell experiment:[1]

Cell lines

Pancreatic cancer cell line PSN-1

Reaction Conditions

6 nM TP-0903 (IC50)

Applications

TP-0903 showed extremely potent activity in cell viability assays with an IC50 of 6 nM against PSN-1 cells. When PSN-1 cells was stimulated by GAS6, TP-0903 was able to dose-dependently decrease phospho-AKT and phospho-AXL levels with an EC50 of 305 and 222 nM, respectively.

Animal experiment:[2]

Animal models

An HCT116 mouse xenograft model and a KRAS-mutant colorectal cancer (CRC) patient-derived xenograft (PDX) mouse model

Dosage form

40 mg/kg

Administered orally

Applications

TP-0903 exhibited 69 and 44% tumor growth inhibition in an HCT116 mouse xenograft model and a KRAS-mutant PDX mouse model, respectively, when administered at a dose of 40 mg/kg.

Note

The technical data provided above is for reference only.

References:

1. Mollard A, Warner SL, Call LT, et al. Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Medicinal Chemistry Letters, 2011, 2(12): 907-912.

2. Mangelson R, Peterson P, Foulks JM, et al. Abstract 2197: The AXL kinase inhibitor, TP-0903, demonstrates efficacy in preclinical models of colorectal cancer independent of KRAS mutation status. Cancer Research, 2019, 79(13 Suppl): Abstract nr 2197.

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