TC-G-1008 (GPR39-C3) is a GPR39 (zinc receptor) agonist (EC50 values are 0.4 and 0.8 nM for rat and human receptors respectively).

GPR139 (human):0.8 nM, rat GPR39
:0.4 nM

TC-G-1008在一系列激酶上显示出选择性(IC50s>10 μM)，且对相关的ghrelin和neurotensin-1受体没有显著的结合亲和力(IC50s>30 μM)[1]。在HEK293-GPR39细胞中，GPR39-C3是一种正向异构调节因子，能激活cAMP产生（Gs下游）、IP1积累（Gq下游）、SRF-RE依赖的转录（G12/13下游）和β-arrestin招募。GPR39-C3通过第二次化合物挑战，以剂量和时间依赖的方式导致对cAMP产生的响应丧失[2]。

TC-G-1008对大鼠和小鼠的血浆蛋白结合率分别为99.3%和99.1%。TC-G-1008是首个强效的GPR39激动剂（人类和大鼠受体的EC50s ≤ 1 nM），能够通过口服在小鼠中生物可用，并显著诱导急性GLP-1水平。经过一次性口服0.5%甲基纤维素/0.1%Tween 80水悬剂中的10、30和100 mg/kg剂量，TC-G-1008在1至1.5小时内分别达到1.4、6.1和25.3 μM的最大暴露水平[1]。

HEK293-GPR39 cells are plated and cultured in poly-d-lysine-coated, white, 384-well plates (4000 cells/well) in the growth medium overnight at 37°C in the presence of 5% CO2. For pretreatment of the cells with GPR39 ligands (TCG-1008) or vehicle control (DMSO), the culture medium is removed and the cells are stimulated with GPR39 ligands in assay buffer for the indicated time at 37°C. Then, the compound solution is removed and washed twice with PBS containing 0.1% BSA. For measurement of intracellular cAMP, the cells are stimulated with drugs in stimulation buffer for 30 min at 37°C. The intracellular cAMP level is determined by using HTRF cAMP dynamic 2 kit[2] .

Mice: Mice are given single oral doses of 10, 30, and 100 mg/kg of TC-G-1008[1] .