Kinasechem是来自英国的专业的抑制剂供应商，提供覆盖几百个激酶靶点的抑制剂。 Kinasechem的产品涉及绝大多数的信号通路研究以及癌症研究，包括： PI3K-Akt signaling pathway； MAPK signaling pathway; apoptosis(凋亡)； DNA damage( DNA 损伤) RTK(受体酪氨酸激酶） 等抑制剂在生命科学研究领域的应用非常广泛。在信号通路以及癌症研究方面，很多地方需要用到抑制剂来阻抑信号通路。目前，在HIV的研究，抗感染，心血管疾病，老年痴呆症（阿兹海默症），甚至糖尿病的研究中，都会使用到抑制剂。 1、 抑制剂的一般使用方法：（1）细胞实验将抑制剂溶解于DMSO, 乙醇或者水中，稀释到需要的浓度。一般孵育48小时，也有孵育2周的实验。（2）动物实验小鼠模型：以注射为主。大鼠模型：以口服为主。（3）抗药性筛选实验长期孵育，递增性增加浓度。 2、抑制剂的几个重要参数： IC50(半抑制浓度) 指抑制剂降低对应激酶的活性到原来活性的一半的浓度。 IC50是抑制剂一个重要的指标，一般而言，IC50越小，抑制能力越强。 EC50 指加入抑制剂后，细胞死亡一半所需的浓度。 抑制剂选择性抑制剂有多重抑制剂，指同时抑制多个靶点的抑制剂。有高选择性抑制剂，仅仅抑制某些激酶的某个亚型或者结构域。比如，有的抑制剂仅仅抑制PI3K这个激酶的gamma亚型。
Information

SKU:K1204		M. Wt:513.61
Formula:C27H27N7O2S		Solubility:DSMO <1 mg/ml Water <1 mg/ml Ethanol <1 mg/ml
Purity:>99%		Storage:2 years at -20 degrees centigrade
CAS No.:1138549-36-6
Chemical Name5H-Benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide, 2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-N-[(5-methyl-2-pyrazinyl)methyl]-5-oxo-

Biological Activity

Description	CX-5461 is a potent small-molecule inhibitor of RNA polymerase (Pol) I.
Targets	Pol I
IC50	54-142 nM
In vitro	CX-5461 is a potent small-molecule inhibitor of RNA polymerase (Pol) I. CX-5461 inhibit Pol I in the HCT-116 cells with IC50 of 142 nM. CX-5461 also inhibit Pol I in melanoma A375 cell line and pancreatic carcinoma MIA PaCa-2 cell line with IC50 of 113 nM and 54 nM.CX-5461 directly targets the Pol I machinery and inhibits Pol I transcription at the initiation stage.CX-5461 inhibits Pol I via disruption of the SL1-rDNA complex. And CX-5461 inhibits Pol I transcription without having an effect on DNA replication, protein translation, and general cellular transcription. As RNA polymerase (Pol) I is a multiprotein complex activated widely in cancer cells, CX-5461 can block cancer cell proliferation. CX-5461 inhibits the initiation stage of rRNA synthesis and induces both senescence and autophagy, but not apoptosis, through a p53-independent process in solid tumor cell lines. For example,CX-5461 induces autophagy but not apoptosis in A375 and MIA Paca-2 cancer cells.[1]
IN vivo	In two murine xenograft models of human cancers, pancreatic carcinoma (MIA PaCa-2) and melanoma (A375), CX-5461(50 mg/kg) demonstrated significant MIA PaCa-2 TGI with TGI equal to 69% on day 31.By inhibiting Pol I transcription, CX-5461 produce in vivo antitumor responses against solid tumors.[1]