Ko 143
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.
Ko 143是一种有效的和选择性的乳腺癌耐药蛋白多药转运体(BCRP)抑制剂,EC90值为26 nM[1]。
BCRP是ATP-结合盒转运蛋白超家族的成员,是一种质膜蛋白,与癌细胞的多药耐药性相关。BCRP存在于肠上皮、肝小管、胎盘滋养层、乳腺导管和小叶,以及静脉和毛细血管的内皮细胞中。MDR是抗癌化疗失败的主要原因,而BCRP可用作广泛特异性的药物外排泵,赋予多药耐药性。当过表达时,BCRP能够赋予各种癌细胞系对药物的耐药性,包括topotecan、doxorubicin、daunorubicin和mitoxantrone。
Ko 143是第一个应用于体内的有效的和特异性的BCRP抑制剂。在小鼠T6400和人T8癌细胞系中进行有效化合物文库筛选时,Ko 143被确定为具有高抑制活性和低细胞毒性的抑制剂。此外,Ko 143对BCRP的选择性比对P-糖蛋白和多药耐药蛋白-1高200倍[2]。在小鼠T6400和人T8癌细胞系中,Ko 143在EC90浓度时还逆转Bcrp-1/BCRP介导的耐药性,导致对topotecan和mitoxantrone 10倍的增敏[2]。
在小鼠模型中,Ko 143以50 mg/day或更高的剂量口服给药后没有急性延迟细胞毒性。在Mdr1a/1b-/-小鼠中,在口服药物后的30 min和60 min时,Ko 143以10 mg/kg的剂量口服给药后增加4-6倍的血浆topotecan水平,表明Ko 143抑制BCRP赋予的多药耐药性[2]。
参考文献:
[1] Loevezijn AV et al. , Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines. Bioorg. Med. Chem. Lett. 2001, 11(1), 29-32.
[2] Allen J D et al. , Potent and Specific Inhibition of the Breast Cancer Resistance Protein Multidrug Transporter in Vitro and in Mouse Intestine by a Novel Analogue of Fumitremorgin C. Mol. Cancer Ther. 2002, 1, 417-425.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 469.59 |
Cas No. | 461054-93-3 |
Formula | C26H35N3O5 |
Synonyms | Ko-143;Ko143 |
Solubility | Soluble in DMSO |
Chemical Name | tert-butyl 3-((3R,6S,12aR)-6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl)propanoate |
SDF | Download SDF |
Canonical SMILES | O=C1N2[C@@H](CC(C)C)C(NC3=C4C=CC(OC)=C3)=C4C[C@@H]2C(N[C@@H]1CCC(OC(C)(C)C)=O)=O |
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 | Ko 143是一种有效的和选择性的乳腺癌耐药蛋白多药转运体(BCRP)抑制剂,EC90值为26 nM。 | |||||
靶点 | BCRP | |||||
IC50 | 26 nM (EC90) |