TP-0903

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TP-0903

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

1341200-45-0

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
50mg	电议
100mg	电议

产品介绍

化学性质

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	516.06
Cas No.	1341200-45-0
Formula	C₂₄H₃₀ClN₇O₂S
Solubility	≥25.8 mg/mL in DMSO with gentle warming; insoluble in EtOH; insoluble in H2O
Chemical Name	2-((5-chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide
Canonical SMILES	CN(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	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。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。

资料参考

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.

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.