LY2784544
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.
LY2784544是一种强效的和选择性的JAK2抑制剂,IC50值为3 nM[1].
Janus激酶2(JAK2)属于Janus激酶家族,是Ⅱ型细胞因子受体家族的成员.它是一种非受体酪氨酸激酶.自身抑制的假性激酶结构域内的JAK2 突变 (V617F)导致功能获得性JAK2激活.JAK2 V617F突变导致随后信号传导子及转录激活子5 (STAT5)的磷酸化.然后,STAT5调节与细胞生长\死亡及分化相关的基因转录.在细胞内,JAK2 V617F突变是致癌的,在小鼠模型内足以产生骨髓增殖性肿瘤(MPN)表型.突变JAK2激酶是骨髓增殖性肿瘤治疗的一个有吸引力的治疗靶标.选择性抑制JAK2 V617F,但对野生型JAK2的抑制最小化将是一个最佳的治疗方法.
LY2784544是一种强效的和ATP竞争性的JAK2酪氨酸激酶抑制剂.LY2784544对JAK2的选择性分别是对JAK1和JAK3的8倍和16倍.相比于 Ba/F3-TEL- JAK3和–JAK1细胞内STAT5的磷酸化,LY2784544能更有效地抑制Ba/F3-TEL-JAK2细胞内STAT5的磷酸化,IC 50值分别为0.191 (JAK2)\2.904 (JAK1) 及4.744 nM (JAK3).在表达JAK2 V617F 的Ba/F3细胞中,浓度范围为50 nM–20 nM的LY2784544显著抑制STAT5磷酸化.另一方面,在IL-3刺激的\表达野生型JAK2的Ba/F3细胞中,浓度为50和200 nM的LY2784544对STAT5磷酸化的抑制作用最小.LY2784544显著抑制表达JAK2 V617F的细胞增殖,IC50值为55 nM.在表达JAK2 V617F的细胞中,LY2784544诱发细胞凋亡,通过Caspase 3/7血清球蛋白实验测得EC50±s.d.的值为113±0.023 nM[1].
LY2784544的TED50(阈值有效剂量50)为12.7 mg/kg,在载Ba/F3-JAK2V617F-GFP的SCID小鼠中,强效抑制STAT5磷酸化.在小鼠血液病模型中,LY2784544也剂量依耐性地降低Ba/F3-JAK2V617F-GFP的肿瘤负荷[1].
参考文献：
1. Ma L, Clayton JR, Walgren RA, Zhao B, Evans RJ, Smith MC, Heinz-Taheny KM, Kreklau EL, Bloem L, Pitou C et al: Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J 2013, 3:e109.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 469.94 |
| Cas No. | 1229236-86-5 |
| Formula | C23H25ClFN7O |
| Solubility | ≥23.5 mg/mL in DMSO; insoluble in H2O; ≥5.65 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-amine |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC(=NN1)NC2=NN3C(=C(N=C3C(=C2)CN4CCOCC4)C)CC5=C(C=C(C=C5)Cl)F |
| 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。 |
| Description | LY2784544是一种高效的和选择性的野生型JAK2和JAK2 V617F突变抑制剂,IC50值分别为2.26 μM 和55 nM. | |||||
| 靶点 | wild-type JAK2 | V617F mutant JAK2 | ||||
| IC50 | 2.26 μM | 55 nM | ||||
化学结构
