TH-302
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
TH-302是一种溴代异磷酰胺氮芥前体药物,由2-硝基咪唑诱发的低氧所激活[1]。
由于肿瘤血管的异常特征与结构,低氧是肿瘤的普遍特征。结果发现,缺氧肿瘤通常耐受传统化疗和放射疗法,具有更强的转移性和侵袭性。因为缺氧肿瘤不是过度增殖的,传统的抗增殖药物并不适用。作为低氧激活的前体药物,TH-302可以释放细胞毒性物质Br-IPM,并在缺氧条件下选择性地将其传输至肿瘤细胞[1,2]。
TH-302的活性依赖于缺氧的程度以及缺氧条件下的药物暴露时间。在更低的氧气浓度下,TH-302具有更高的活性。与Tirapazamine(另一种HAP)不同,TH-302需要更苛刻的缺氧环境(约0.1%),以保持其高效能。在32种肿瘤细胞中,TH-302在正常空气条件下显示出适度的细胞毒性,其IC50值均高于40 μM。相比之下,TH-302在缺氧状态下具有更高的抗肿瘤效能,其IC50范围为0.1 ~ 90 μM。在这些肿瘤细胞中,非小细胞肺癌H460细胞对TH-302治疗最敏感,IC50值为0.1±0.03 μM。此外,TH-302对一系列其它肿瘤细胞也显现出强效能,包括Caki-1(肾)、SK-MEL-5(黑素瘤)、DU145(前列腺)和HCT116(结肠癌),对应的IC50值为0.4、0.7、0.7和0.8 μM[1]。
在H460细胞异种移植的小鼠模型中,给予6.25 ~ 50 mg/kg的TH-302呈剂量依赖性引起43% ~ 89%的肿瘤生长抑制(TGI),而给予50 mg/kg的TH-302没有表现出血液毒性。此外,结果发现,TH-302诱导DNA损伤。给予100 mg/kg的TH-302,于6小时后,γH2AX阳性细胞显著增加[2]。
参考文献:
[1] Meng F, Evans J W, Bhupathi D, et al. Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302. Molecular cancer therapeutics, 2012, 11(3): 740-751.
[2] Sun J D, Liu Q, Wang J, et al. Selective tumor hypoxia targeting by hypoxia-activated prodrug TH-302 inhibits tumor growth in preclinical models of cancer. Clinical cancer research, 2012, 18(3): 758-770
.Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 449.04 |
Cas No. | 918633-87-1 |
Formula | C9H16Br2N5O4P |
Synonyms | TH 302,TH302,HAP-302,HAP302 |
Solubility | ≥22.45 mg/mL in DMSO; ≥34.2 mg/mL in EtOH with ultrasonic; ≥4.73 mg/mL in H2O with gentle warming and ultrasonic |
Chemical Name | 2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine |
SDF | Download SDF |
Canonical SMILES | CN1C(=CN=C1[N+](=O)[O-])COP(=O)(NCCBr)NCCBr |
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。 |
描述 | TH-302是细胞毒素溴代异磷酰胺氮芥(Br-IPM)的低氧激活前体药物。 | |||||
靶点 | thioredoxin reductase | glutathione reductase | ||||
IC50 |
质量控制和MSDS
- 批次: