| CAS NO: | 200484-11-3 |
| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 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。 |
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.
| 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. | |
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