GMX1778(CHS828)

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GMX1778(CHS828)

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

200484-11-3

包装与价格：

包装	价格(元)
10mM (in 1mL DMSO)	电议
10mg	电议
50mg	电议

产品介绍

化学性质

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	371.86
Cas No.	200484-11-3
Formula	C₁₉H₂₂ClN₅O
Solubility	insoluble in H2O; insoluble in EtOH; ≥18.3 mg/mL in DMSO
Chemical Name	(Z)-2-(6-(4-chlorophenoxy)hexyl)-1-cyano-3-(pyridin-4(1H)-ylidene)guanidine
Canonical SMILES	ClC1=CC=C(OCCCCCC/N=C(\N=C2C=CNC=C/2)NC#N)C=C1
运输条件	蓝冰运输或根据您的需求运输。
一般建议	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。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。

资料参考

GMX1778（CHS828）是烟酰胺磷酸（NAMPT）的特异性抑制剂，Kd值为120 nM [1]。

NAMPT是NAD+生物合成酶。NAD+是酶氧化还原反应的辅因子，参与包括ATP产生的细胞代谢。 NAD+参与许多细胞通路，例如基因调控、钙稳态、基因组的完整性、长寿和凋亡。癌细胞显著依赖于NAD+所提供的高水平的ATP产量，从而来快速实现细胞增殖[1]。

30 nM的GMX1778处理6小时后，与未经处理的细胞胞质提取物相比，IM-9细胞的提取物中NAD+和NM水平降低。整个实验的时间过程中，这些物质的含量持续减少。产生最大改变的是代谢产物NAD+的水平。在6到20小时之间，NAD +的含量下降[1]。

NAD+补救途径会生成NAD+，用作烟酸（NA）或烟酰胺（NM）的底物。 NAPRT1是NA磷酸核糖转移酶1的缩写，在含有丰富NAPRT1的HCT-116细胞系和NAPRT1缺陷的HT1080小鼠细胞系中，静脉注射150 mg/kg或50 mg/kg GMX1777 24小时，产生抗肿瘤活性。在NAPRT1缺陷异种移植模型中，4小时静脉输注120 mg/kg 的NA，对GMX1777的抗肿瘤活性未产生不利的影响，但消除了含有丰富NAPRT1的HCT-116细胞系中GMX1777的抗肿瘤活性[1]。

参考文献：
[1]. Watson M, Roulston A, Bélec L, et al. The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors. Molecular and cellular biology, 2009, 29(21): 5872-5888.

试验操作

Cell experiment:[1]
Cell lines	IM-9 cells
Reaction Conditions	30 nM GMX1778 for 6 h incubation
Applications	Treatment with 30 nM GMX1778 for 6 h decreased NAD+ and nicotinamide (NM) levels in IM-9 cells, which continued to decrease throughout the rest of the time course experiment. The metabolite NAD⁺level was found to be the most profoundly changed, and the NAD+ decline occurred between the 6- and 20-h time points.
Animal experiment:[2]
Animal models	Nude mice bearing midgut carcinoid (GOT1), pancreatic carcinoid (BON) and medullary thyroid cancer (GOT2) tumors
Dosage form	100 or 250 mg/kg/week Administered orally (p.o,)
Applications	GMX1778 (250 mg/kg, p.o.) showed marked antitumor activity against three different human neuroendocrine tumors transplanted in nude mice. Histological examination of all three tumor types showed that in the high-dose group, necrosis was the predominant mode of cell death, although apoptotic cells were also found.
Note	The technical data provided above is for reference only.
	References: 1. Watson M, Roulston A, Bélec L, et al. The small molecule GMX1778 is a potent inhibitor of NAD⁺biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors. Molecular and Cellular Biology, 2009, 29(21): 5872-5888. 2. Johanson V, Arvidsson Y, Kolby L, et al. Antitumoural effects of the pyridyl cyanoguanidine CHS 828 on three different types of neuroendocrine tumours xenografted to nude mice. Neuroendocrinology, 2005, 82(3-4): 171-176.