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VU0364770
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。
VU0364770图片
CAS NO:61350-00-3
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品介绍
VU0364770 是一种有效的选择性mGlu4正变构调节剂 (PAM)。VU0346770 对大鼠 mGlu4 和人 mGlu4 受体的EC50分别为 290 nM 和 1.1 μM。VU0364770 对 mGlu5 具有拮抗活性,EC50为 17.9 μM,VU0364770 对 mGlu6 具有正变构调节活性,EC50为 6.8 μM。VU0364770 还对 MAO 具有活性,作用于人 MAO-A 和 MAO-B 的 Ki值分别为8.5 和 0.72 μM。
生物活性

VU0364770 is a selective and potent positive allosteric modulator (PAM) ofmGlu4. VU0346770 exhibitsEC50s of 290 nM and 1.1 μM atrat mGlu4andhuman mGlu4 receptor, respectively. VU0364770 exhibits antagonist activity at mGlu5 with a potency of 17.9 μM and PAM activity at mGlu6 with a potency of 6.8 μM. VU0364770 also possesses activity at MAO with Kivalues of 8.5 and 0.72 μM for humanMAO-Aand humanMAO-B, respectively[1].

IC50& Target[1]

Rat mGlu4

290 nM (EC50)

Human mGlu4

1.1 μM (EC50)

mGlu6

6.8 μM (EC50)

mGlu5

17.9 μM (EC50)

体外研究
(In Vitro)

VU0364770 is a selective positive allosteric modulator of mGlu4in recombinant systems. VU0364770 is a potent PAM of multiple signaling pathways that enhances the response of the rat and human mGlu4receptors to the endogenous agonist glutamate. VU0364770 produces a concentration-dependent potentiation of the response to an EC20concentration of glutamate with EC50of 1.1±0.2 μM and increases the maximal response to glutamate from 100 to 227±17%. Because of concerns that this chemical scaffold might possess activity at MAO, full IC50determinations is performed for VU0364770 at the MAO-A and MAO-B isoforms; these studies result in Kis of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively. When tested at a 10 μM concentration at each mGlu receptor, VU0364770 exhibits weak PAM activity (4.3-fold left shift of the glutamate CRC) at mGlu6 and antagonist activity (3.3-fold right shift of the glutamate CRC) at mGlu5 (compare to the 16.5-fold left shift of the glutamate concentration-response for mGlu4at 10 μM). When further evaluated in a full concentration-response curve format, VU0364770 exhibits antagonist activity at mGlu5with a potency of 17.9±5.5 μM and PAM activity at mGlu6with a potency of 6.8±1.7 μM (compare with the potency of VU0364770 on the rat mGlu4receptor of 290±80 nM)[1].

体内研究
(In Vivo)

VU0364770 exhibits suitable pharmacokinetic properties for systemic dosing in animal models. After intravenous administration, VU0364770 is rapidly clears from the systemic circulation (165 ml/min/kg) and exhibits a volume of distribution of 2.92 L/kg. VU0364770 is a highly protein-bound ligand displaying free fractions of 2.7 and 1.8% in human and rat plasma, respectively. VU0364770 also shows an improved pharmacokinetic profile relative to previously reported mGlu4PAMs with enhanced central penetration and a total brain-to-plasma ratio of more than 1 after systemic administration of a 10 mg/kg dose. VU0364770 produces a dose-dependent reversal of haloperidol-induced catalepsy. VU0364770 dose-dependently reverses haloperidol (0.75 mg/kg)-induced catalepsy in rats, significant at doses of 10 to 56.6 mg/kg, after subcutaneous dosing (F6,69=8.04; p<0.001)[1].

分子量

232.67

性状

Solid

Formula

C12H9ClN2O

CAS 号

61350-00-3

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : ≥ 100 mg/mL(429.79 mM)

*"≥" means soluble, but saturation unknown.

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM4.2979 mL21.4897 mL42.9793 mL
5 mM0.8596 mL4.2979 mL8.5959 mL
10 mM0.4298 mL2.1490 mL4.2979 mL
*

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℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (10.74 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (10.74 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90%corn oil

    Solubility: ≥ 2.5 mg/mL (10.74 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (10.74 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在本网站选购。