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:K1113		M. Wt:405.42
Formula:C20H22F3N5O		Solubility:DSMO 81 mg/mL Water <1 mg/ml Ethanol 81 mg/mL
Purity:>99%		Storage:2 years at -20 degrees centigrade
CAS No.:1025065-69-3
Chemical NameN-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine

Biological Activity

Description	SGI-1776 free base can inhibit Pim1, Pim2, and Pim3 with IC50 of 7 nM, 363 nM and 9 nM.
Targets	Pim1	Pim2	Pim3
IC50	7 nM	363 nM	9 nM
In vitro	SGI-1776 can potently inhibit Pim-1, Pim-2 and Pim-3 with IC50 of 7 nM, 363 nM and 69 nM. SGI-1776 also can inhibit Flt-3 and haspin with IC50 of 44 nM and 34 nM. SGI-1776, as an inhibitor of PIM kinase, shows inhibition to B-cell chronic lymphocytic leukemia (CLL). Pim kinases are over-expressed in B-cell chronic lymphocytic leukemia and inhibition of Pim kinases can affect the survival of B- cell. Besides inhibition to Pim kinases, the level of Mcl-1 protein can be markedly reduced by SGI-1776. Besides inhibition to kinases, SGI-1776 also shows inhibition to RNA synthesis. SGI-1776 can decrease in total RNA synthesis to approximately 50% of control at 10 umol/L.
IN vivo	In AML cell lines (1) SGI-1776 can decrease phosphorylation of c-Myc and 4E-BP1. c-Myc(Ser62) phosphorylation was decreased by 50% relative to control at 0.1uM SGI-1776, which was further reduced by 80% with 1 uM. In MOLM-13 and OCI-AML-3 cell lines, and there was a signi?cant reduction in c-Myc phosphorylation after treatment with SGI-1776. Phosphorylation of translation regulator 4E-BP1 (Thr37/Thr46) was also decreased at 0.1uM SGI-1776 treatment in MV-4-11, MOLM-13 and OCI-AML-3. (2) SGI-1776 can induce apoptosis in AML cell lines. There was a dose-dependent increase in apoptotic cells after treatment with SGI-1776, and there was 25% increase in apoptosis with 10 uM SGI-1776. (3) The inhibition to FLT3-ITD by SGI-1776 is as potent as the inhibition to FLT3-ITD by AC220 in AML cell lines.