NKP608
(Synonyms: (2R,4S)-N-[1-[3,5-双(三氟甲基)苯甲酰]-2-(4-氯苄基)哌啶-4-基]喹啉-4-甲酰胺) 目录号 : GC36749
NKP608为非肽类4-氨基哌啶衍生物，是神经激肽-1（NK-1）受体拮抗剂，IC50为2.6 nM。
Cas No.:177707-12-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
NKP608 is a non-peptidic derivative of 4-aminopiperidine which acts as a selective, specific and potent antagonist at the neurokinin-1 (NK-1) receptor both in vitro(IC50=2.6 nM) and in vivo. IC50 value: 2.6 nMTarget: NK-1 receptorIn vitro, the binding of NKP608 to bovine retina was characterized by an IC50 of 2.6+/-0.4 nM, whereas the compound's affinity to other receptor binding sites, including NK-2 and NK-3, was much lower. Species differences in IC(50) values with NKP608 were less pronounced than with previously described NK-1 receptor antagonists, being 13+/-2 and 27+/-2 nM in gerbil midbrain and rat striatum, respectively. In vivo, using the hind foot thumping model in gerbils, NKP608 exhibited a potent NK-1 antagonistic activity following oral administration (ID(50)=0.23 mg/kg; 2 h pretreatment), supporting a central activity of NKP608. NKP608 may prove a useful anxiolytic compound.
[1]. El-Hashim AZ, Wyss D, Lewis C. Effect of a novel NK1 receptor selective antagonist (NKP608) on citric acid induced cough and airway obstruction. Pulm Pharmacol Ther. 2004;17(1):11-8. [2]. Vendruscolo LF, Takahashi RN, BrÜske GR, Ramos A. Evaluation of the anxiolytic-like effect of NKP608, a NK1-receptor antagonist, in two rat strains that differ in anxiety-related behaviors. Psychopharmacology (Berl). 2003 Nov;170(3):287-93. [3]. Rupniak NM, Carlson EJ, Shepheard S, et al. Comparison of the functional blockade of rat substance P (NK1) receptors by GR205171, RP67580, SR140333 and NKP-608. Neuropharmacology. 2003 Aug;45(2):231-41. [4]. Gentsch C, Cutler M, Vassout A, et al. Anxiolytic effect of NKP608, a NK1-receptor antagonist, in the social investigation test in gerbils. Behav Brain Res. 2002 Jul 18;133(2):363-8. [5]. Vassout A, Veenstra S, Hauser K, et al. NKP608: a selective NK-1 receptor antagonist with anxiolytic-like effects in the social interaction and social exploration test in rats. Regul Pept. 2000 Dec 22;96(1-2):7-16.
| Cas No. | 177707-12-9 | SDF | |
| 别名 | (2R,4S)-N-[1-[3,5-双(三氟甲基)苯甲酰]-2-(4-氯苄基)哌啶-4-基]喹啉-4-甲酰胺 | ||
| Canonical SMILES | O=C(C1=CC=NC2=CC=CC=C12)N[C@@H]3C[C@@H](CC4=CC=C(Cl)C=C4)N(C(C5=CC(C(F)(F)F)=CC(C(F)(F)F)=C5)=O)CC3 | ||
| 分子式 | C31H24ClF6N3O2 | 分子量 | 619.98 |
| 溶解度 | DMSO: 100 mg/mL (161.30 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.613 mL | 8.0648 mL | 16.1296 mL |
| 5 mM | 0.3226 mL | 1.613 mL | 3.2259 mL |
| 10 mM | 0.1613 mL | 0.8065 mL | 1.613 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
NKP608: a selective NK-1 receptor antagonist with anxiolytic-like effects in the social interaction and social exploration test in rats
Regul Pept 2000 Dec 22;96(1-2):7-16.PMID:11102646DOI:10.1016/s0167-0115(00)00194-4.
NKP608 is a non-peptidic derivative of 4-aminopiperidine which acts as a selective, specific and potent antagonist at the neurokinin-1 (NK-1) receptor both in vitro and in vivo. In vitro, the binding of NKP608 to bovine retina was characterized by an IC50 of 2.6+/-0.4 nM, whereas the compound's affinity to other receptor binding sites, including NK-2 and NK-3, was much lower. Species differences in IC(50) values with NKP608 were less pronounced than with previously described NK-1 receptor antagonists, being 13+/-2 and 27+/-2 nM in gerbil midbrain and rat striatum, respectively. In vivo, using the hind foot thumping model in gerbils, NKP608 exhibited a potent NK-1 antagonistic activity following oral administration (ID(50)=0.23 mg/kg; 2 h pretreatment), supporting a central activity of NKP608. The compound had a long duration of action with an ID(50) value of 0. 15 mg/kg p.o. and 0.38 mg/kg p.o. following a pretreatment of 5 and 24 h, respectively. Following a subchronic administration for 7 consecutive days (once daily) there was no evidence for the development of tolerance or accumulation. In the social interaction test performed in a highly illuminated, unfamiliar test arena, NKP608 specifically increased the time the two rats spent in social contact, and there was no concomitant increase in parameters reflecting general activity, i.e. ambulation (number of square entries) or the number of rearings. Active social time was maximally increased at a dose range of 0.01-1 mg/kg p.o. NKP608, the effect being weaker or absent at both lower (0.001 mg/kg p.o.) and higher (10 mg/kg p.o.) doses. A comparable bell-shaped dose-response relation was seen in the social exploration test in rats. In this modified resident/intruder paradigm, maximal increase in social contact of the intruder rat directed towards the resident rat was seen at a similar dose range (0.03-3 mg/kg p.o.) The effects observed following an acute oral administration of NKP608 were comparable to those seen following a treatment with the well-known benzodiazepine, chlordiazepoxide, in both these tests. These findings indicate that NKP608 exhibits an anxiolytic-like effect and that this effect, as concluded from the observed antagonism of the hind foot thumping induced by i.c.v. administration of the NK-1 receptor agonist SPOMe, is centrally mediated. This makes this compound a potentially promising candidate for treating anxiety-related disorders in humans.
The NK1 receptor antagonist NKP608 inhibits proliferation of human colorectal cancer cells via Wnt signaling pathway
Biol Res 2018 May 30;51(1):14.PMID:29843798DOI:10.1186/s40659-018-0163-x.
Background: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism. Methods: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot. Results: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, β-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3. Conclusions: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/β-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.
NKP608, an NK1 receptor antagonist, has an anxiolytic action in the social interaction test in rats
Psychopharmacology (Berl) 2000 Sep;152(1):105-9.PMID:11041322DOI:10.1007/s002130000513.
Rationale: Evidence is starting to accumulate that NK1 receptor antagonists might have anxiolytic effects in animal tests and in patients. Objective: To examine the effects of NKP608, a substance P antagonist acting at NK1 receptors, in various conditions of the social interaction test of anxiety and to determine its effects after 3 and 6 weeks of treatment. Methods: Rats were tested after vehicle, 0.01 or 0.1 mg/kg PO in three conditions of the social interaction test that varied in the level of anxiety generated. Thus pairs of rats were tested in an arena with which they were unfamiliar that was lit by high (HU) or low (LU) light and in the condition that generated the lowest level of anxiety, i.e. an arena with which they were familiar, lit by low light (LF). They were also tested after 3 and 6 weeks of treatment with 0.03 mg/kg and after 24 h withdrawal from these chronic treatments. Results: NKP608 had significant anxiolytic effects at 0.01, 0.03 and 0.1 mg/kg PO in the HU and LU test conditions, but was without effect in the LF condition, except for an increased incidence of bite attacks at 0.1 mg/kg. The anxiolytic effect of 0.03 mg/kg remained after 3 weeks of chronic treatment and there was no anxiogenic effect after 24 h of drug withdrawal. Following 6 weeks of chronic treatment (0.03 mg/kg per day), tolerance had developed, but no anxiogenic withdrawal effect was seen 24 h after the last dose. Conclusions: These results provide further evidence that substance P may play a role in mediating states of anxiety and suggest that the selective NK1 receptor antagonist NKP608 may prove a useful anxiolytic compound.
The NK1-receptor antagonist NKP608 has an antidepressant-like effect in the chronic mild stress model of depression in rats
Behav Brain Res 2000 Oct;115(1):19-23.PMID:10996404DOI:10.1016/s0166-4328(00)00230-8.
The chronic mild stress (CMS) model of depression was used to study the potential antidepressant-like activity of NKP608, a non-peptidic, specific, potent and orally active NK1 receptor antagonist. In this model, a substantial decrease in consumption of a 1% sucrose solution is observed in rats continously subjected to a variety of mild stressors. This effect can be reversed by chronic administration of various classes of antidepressant drugs. Chronic, oral treatment with NKP608 (once daily for 5 weeks) gradually reversed CMS-induced reductions in sucrose consumption and, the magnitude of this effect was comparable to that observed following administration of imipramine (10 mg/kg). The time-course of action of NKP608 in the CMS model was dose-dependent. At the dose of 0.03 mg/kg, NKP608 caused a full reversal of the CMS-induced deficit in sucrose consumption after 4 weeks of treatment (comparable to 5 weeks required for imipramine), while only 1 week of treatment was required in the group receiving the dose of 0.1 mg/kg NKP608. Lower (0.003 mg/kg) and higher (1.0 mg/kg) doses of the compound were ineffective. These results suggest that NKP608 has antidepressant-like properties in the CMS model in rats; the effect was comparable to conventional drugs, but the onset of action was faster than with the representative tricyclic antidepressant imipramine.
Evaluation of the anxiolytic-like effect of NKP608, a NK1-receptor antagonist, in two rat strains that differ in anxiety-related behaviors
Psychopharmacology (Berl) 2003 Nov;170(3):287-293.PMID:12915956DOI:10.1007/s00213-003-1545-4.
Rationale: NKP608, a selective NK1 receptor antagonist, has been shown to produce anxiolytic-like effects in rodents tested in different anxiety models. However, most of these findings are based on social behaviors and, to our knowledge, there is no report concerning the effects of NKP608 in the elevated plus-maze (EPM) and the open field (OF), two classical models of anxiety/emotionality. Moreover, this compound has never been tested in rodent strains that display contrasting levels of anxiety-related behaviors. Objectives: To investigate the anxiolytic-like effects of NKP608 in Lewis and SHR inbred rats, proposed as a genetic model of anxiety for showing high and low indices of anxiety, respectively. Methods: Lewis and SHR rats of both sexes were tested in the EPM and OF tests following acute administration of NKP608 (0.003, 0.03 or 0.3 mg/kg) or chlordiazepoxide (CDZ, 5 mg/kg). Measures of approach/avoidance towards the open arms of the EPM and the central area of the OF were used as indices of anxiety. Results: All doses of NKP608 produced anxiolytic-like effects, similar to those of CDZ, in SHR males tested in the OF but not in the EPM. Conversely, this compound had a partial anxiolytic effect in LEW males (and, to a lower degree, in SHR females) in the EPM, but not in the OF. LEW females were unaffected following all pharmacological treatments. Conclusions: These findings indicate that the anxiety-related effects of NKP608 are strain-, sex- and test-dependent. Moreover, the present data confirm and extend the therapeutic potential of NK1 receptor antagonists for the treatment of anxiety.