GPCR
联系我们GPCR是一类重要的成药性靶点，超过800个成员，是大的成药性靶点家族。FDA批准的药物中，超过25%的药物作用于GPCR靶点。根据下游信号差异，爱思益普建立了基于荧光的多种筛选方法和平台，已经构建和正在优化的GPCR受体超过150个，并正在快速扩大，可以按客户需求定制。
GPCR靶点化合物的分析手段：
l HTRF cAMP/IP1
l Calcium Flux/FLIPR
l 荧光素酶报告基因
l Tag-lite Binding
l Flow Cytometry
l …..
HTRF cAMP/IP1检测GPCR
图1. 重组GLP-1受体在HTRF cAMP/IP1检测系统中对激动剂/抑制剂的浓度响应曲线。
用相应配体处理后使用BMG酶标仪读取荧光值的变化。
Calcium Flux/FLIPR 检测GPCR
图2. 重组H1受体在钙流检测系统中对激动剂/抑制剂的浓度响应曲线。
用相应配体处理后使用FLIPR读取钙离子指示剂荧光值的变化。
荧光素酶报告基因系统检测GPCR
CRE/reporter genes (luciferase, b-lactamase)
NFAT/reporter genes
SRE/ reporter genes
图3. HEK293/CRE-reporter genes稳定细胞株共转GLP-1R后的配体响应曲线。
用BMG多功能酶标仪检测配体处理后报告基因与底物反应后的荧光值变化。
Tag-Lite 方法检测GPCR与配体结合
图4. HEK293/SNAP-AT2稳定细胞株与荧光配体的响应曲线。
用BMG多功能酶标仪检测配体处理后的荧光值变化。
Flow Cytometry 方法检测GPCR与配体的结合
图5. HEK293/GPCR稳定细胞株与荧光配体的响应曲线。
用Flow Cytometry检测配体处理后的细胞的荧光值变化。
爱思益普能够提供快速高效的化合物分析服务，以确定各自的激动和抑制活性以及先导化合物对各种药物靶点的选择性，帮助您加快化合物在hit-to-lead的选择过程。
GPCR靶点List
|
Receptor Family |
Receptor |
Species |
Mode |
|
Adenosine |
A1 |
human |
Agonist |
|
A2A |
human |
Agonist and Antagonist |
|
|
A2B |
human |
Agonist |
|
|
A3 |
human |
Agonist |
|
|
Adrenoceptors |
Alpha 1A |
human |
Agonist and Antagonist |
|
Alpha 1B |
human |
Agonist and Antagonist |
|
|
Alpha 1D |
human |
Agonist and Antagonist |
|
|
Alpha 2A |
human |
Agonist and Antagonist |
|
|
Alpha 2B |
human |
Agonist and Antagonist |
|
|
Alpha 2C |
human |
Agonist and Antagonist |
|
|
Beta 1 |
human |
Agonist and Antagonist |
|
|
Beta 2 |
human |
Agonist and Antagonist |
|
|
Cannabinoid |
CB1 |
human |
Agonist and Antagonist |
|
CB2 |
human |
Agonist and Antagonist |
|
|
Chemokine |
CCR1 |
human |
Agonist and Antagonist |
|
CCR2 |
human |
Agonist |
|
|
CCR5 |
human |
Agonist and Antagonist |
|
|
CCR6 |
human |
Agonist |
|
|
CCR7 |
human |
Agonist |
|
|
CCR8 |
human |
Agonist and Antagonist |
|
|
CCR9A |
human |
Agonist |
|
|
CCR9B |
human |
Agonist |
|
|
CXCR1 |
human |
Agonist and Antagonist |
|
|
CXCR2 |
human |
Agonist and Antagonist |
|
|
CXCR3 |
human |
Agonist |
|
|
CXCR4 |
human |
Agonist and Antagonist |
|
|
CXCR5 |
human |
Agonist |
|
|
Cholecystokinin |
CCK1 |
human |
Agonist and Antagonist |
|
CCK2 |
human |
Agonist and Antagonist |
|
|
Dopamine |
D1 |
human |
Agonist and Antagonist |
|
D2L |
human |
Agonist and Antagonist |
|
|
D2S |
human |
Agonist and Antagonist |
|
|
D3 |
human |
Agonist and Antagonist |
|
|
D4 |
human |
Agonist and Antagonist |
|
|
D5 |
human |
Agonist and Antagonist |
|
|
Endothelin |
ETA |
human |
Agonist and Antagonist |
|
ETB |
human |
Agonist and Antagonist |
|
|
rat ETB |
Rat |
Agonist and Antagonist |
|
|
mouse ETB |
mouse |
Agonist and Antagonist |
|
|
dog ETB |
dog |
Agonist and Antagonist |
|
|
Glucagon |
GCGR |
human |
Agonist and Antagonist |
|
mouse GCGR |
mouse |
Agonist and Antagonist |
|
|
rat GCGR |
Rat |
Agonist and Antagonist |
|
|
GLP-1R |
human |
Agonist and Antagonist |
|
|
mouse mGLP-1R |
mouse |
Agonist and Antagonist |
|
|
rat GLP-1R |
Rat |
Agonist and Antagonist |
|
|
dog GLP1R |
Dog |
Agonist and Antagonist |
|
|
macaca GLP1R |
Monkey |
Agonist and Antagonist |
|
|
rabbit GLP1R |
Rabbit |
Agonist and Antagonist |
|
|
GLP-2R |
human |
Agonist |
|
|
GIPR |
human |
Agonist and Antagonist |
|
|
dog GIPR |
Dog |
Agonist and Antagonist |
|
|
monkey GIPR |
Monkey |
Agonist and Antagonist |
|
|
mouse GIPR |
mouse |
Agonist and Antagonist |