| CAS |
No.1621175-65-2 |
| 英文名称 |
TC-G-1008 |
| 分子式 |
C18H19ClN6O2S |
| 分子量 |
418.9 |
| 溶解性 |
Soluble in DMSO ≥10mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD30182283 |
| SMILES |
CNC1=NC(=CC(=N1)NCC2=C(C=C(C=C2)NS(=O)(=O)C)Cl)C3=CC=CC=N3 |
| InChIKey |
DRSZMILOMUPIBJ-UHFFFAOYSA-N |
| InChI |
InChI=1S/C18H19ClN6O2S/c1-20-18-23-16(15-5-3-4-8-21-15)10-17(24-18)22-11-12-6-7-13(9-14(12)19)25-28(2，26)27/h3-10，25H，11H2，1-2H3，(H2，20，22，23，24) |
| PubChem CID |
91826086 |
| 靶点 |
GPR39 |
| 通路 |
GPCR & G Protein |
| 背景说明 |
TC-G-1008是一种有效的，有口服活性的 GPR39 激动剂。 |
| 生物活性 |
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.[1-2] |
| IC50 |
IC50: 0.4 nM (GPR39)， 0.8 nM (GPR39)[1] |
| In Vitro |
TC-G-1008 shows selectivity over a panel of kinases (IC50s>10 μM) and does not exhibit relevant binding affinity for the related ghrelin and neurotensin-1 receptors (IC50s>30 μM)[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]. |
| In Vivo |
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 μM， respectively[1]. |
| 动物实验 |
Mice: Mice are given single oral doses of 10， 30， and 100 mg/kg of TC-G-1008[1]. |
| 激酶实验 |
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]. |
| 数据来源文献 |
[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. |
| 规格 |
1mg 2mg 5mg 10mg 25mg |
| 单位 |
瓶 |
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