GMX1778 (CHS828)
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.
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.
| 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 |
| SDF | Download SDF |
| 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 | 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。 |
| Cell experiment:[1] | |
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Cell lines |
IM-9 cells |
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Reaction Conditions |
30 nM GMX1778 for 6 h incubation |
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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] | |
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Animal models |
Nude mice bearing midgut carcinoid (GOT1), pancreatic carcinoid (BON) and medullary thyroid cancer (GOT2) tumors |
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Dosage form |
100 or 250 mg/kg/week Administered orally (p.o,) |
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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. |
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Note |
The technical data provided above is for reference only. |
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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, Kölby 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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质量控制和MSDS
- 批次:
化学结构
