TC-G-1008
(Synonyms: GPR39-C3) 目录号 : GC19349A potent GPR39 agonist
Cas No.:1621175-65-2
Sample solution is provided at 25 µL, 10mM.
TC-G-1008 (GPR39-C3) is a potent and orally available GPR39 agonist with EC50 values of 0.4 and 0.8 nM for rat and human receptors respectively.
TC-G-1008 shows selectivity over a panel of kinases (IC50s>10 uM) and does not exhibit relevant binding affinity for the related ghrelin and neurotensin-1 receptors (IC50s>30 uM)[1]. In HEK293-GPR39 cells, GPR39-C3, which is a positive allosteric modulator, activates cAMP production (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment. GPR39-C3 induces dose- and time-dependent loss of response in cAMP production by second challenge of the compound[2].
Rat and mouse plasma protein binding for TC-G-1008 is measured as 99.3% and 99.1%, respectively. TC-G-1008 is orally bioavailable in mice and robustly induces acute GLP-1 levels. Upon single oral doses of 10, 30, and 100 mg/kg of aqueous suspensions in 0.5% methylcellulose/0.1% Tween 80, TC-G-1008 achieves, between 1 and 1.5 h, maximal exposures of 1.4, 6.1, and 25.3 uM, respectively[1].
References:
[1]. Peukert S, et al. Discovery of 2-Pyridylpyrimidines as the First Orally Bioavailable GPR39 Agonists. ACS Med Chem Lett. 2014 Aug 4;5(10):1114-8.
[2]. Shimizu Y, et al. Rho kinase-dependent desensitization of GPR39; a unique mechanism of GPCR downregulation. Biochem Pharmacol. 2017 Sep 15;140:105-114.
Kinase experiment: | 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 (TC-G-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]. |
Animal experiment: | Mice: Mice are given single oral doses of 10, 30, and 100 mg/kg of TC-G-1008[1]. |
References: [1]. Peukert S, et al. Discovery of 2-Pyridylpyrimidines as the First Orally Bioavailable GPR39 Agonists. ACS Med Chem Lett. 2014 Aug 4;5(10):1114-8. |
Cas No. | 1621175-65-2 | SDF | |
别名 | GPR39-C3 | ||
Canonical SMILES | CS(=O)(NC1=CC=C(CNC2=NC(NC)=NC(C3=NC=CC=C3)=C2)C(Cl)=C1)=O | ||
分子式 | C18H19ClN6O2S | 分子量 | 418.9 |
溶解度 | DMSO : ≥ 100 mg/mL (238.72 mM) | 储存条件 | Store at -20°C |
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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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.3872 mL | 11.936 mL | 23.872 mL |
5 mM | 0.4774 mL | 2.3872 mL | 4.7744 mL |
10 mM | 0.2387 mL | 1.1936 mL | 2.3872 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 | |||
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% 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。
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Quality Control & SDS
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- Purity: >99.00%
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