ARRY-520 R enantiomer
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.
纺锤体驱动蛋白(KSP)是参与有丝分裂前期阶段负责中心体分离的有丝分裂驱动蛋白成员之一。作为ARRY-520的R型,ARRY-520 R对映体是一种合成的小分子KSP抑制剂。
体外:ARRY-520在各种肿瘤细胞系中具有低纳摩尔的抗增殖活性,在多药耐药细胞系中也具有活性。在HCT-15、NCI/ADR-RES及K562/ADR细胞中,ARRY-520抑制增殖的EC50值分别为3.7、14及4.2 nM,然而在这些细胞系中紫杉醇的EC50值分别为35、565及372 nM。此外,K562/ADR对紫杉醇的耐药性是亲本细胞系K562的118倍,但仅是ARRY-520的3.5倍[1]。
体内:ARRY-520在UISO-BCA-1异种移植物中有活性,而该异种移植物对紫杉醇有完全耐药性。在HT-29、 HCT-116、MDA-MB-231及A2780异种移植小鼠中,ARRY-520的抗肿瘤功效优于紫杉醇。在雄激素受体阴性前列腺癌PC-3异种移植模型及DU145前列腺癌异种移植模型中,ARRY-520均优于多西他赛。
临床试验:进行I期临床试验,建立ARRY-520的安全性和最大耐受剂量(MTD)。两种剂量方案的每周期总剂量MTD为4.5 mg/m2。剂量限制性毒性包括剥脱性皮疹、手足综合症、粘膜炎及高胆红素血症。在36名患者的33名中观察到3或4级可逆性药品相关骨髓抑制情况。
参考文献:
[1] Woessner R, Tunquist B, Lemieux C, Chlipala E, Jackinsky S, Dewolf W Jr, Voegtli W, Cox A, Rana S, Lee P, Walker D. ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models. Anticancer Res. 2009;29(11):4373-80.
[2] Khoury HJ, Garcia-Manero G, Borthakur G, Kadia T, Foudray MC, Arellano M, Langston A, Bethelmie-Bryan B, Rush S, Litwiler K, Karan S, Simmons H, Marcus AI, Ptaszynski M, Kantarjian H. A phase 1 dose-escalation study of ARRY-520, a kinesin spindle protein inhibitor, in patients with advanced myeloid leukemias. Cancer. 2012;118(14):3556-64.
Storage | Store at -20°C |
M.Wt | 420.48 |
Cas No. | 885060-08-2 |
Formula | C20H22F2N4O2S |
Solubility | Soluble in DMSO |
Chemical Name | (2R)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3-carboxamide |
SDF | Download SDF |
Canonical SMILES | CN(C(=O)N1C(SC(=N1)C2=C(C=CC(=C2)F)F)(CCCN)C3=CC=CC=C3)OC |
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。 |