1621175-65-2
1621175-65-2 structure
- Name: TC-G 1008
- Chemical Name: N-[3-Chloro-4-({[2-(methylamino)-6-(2-pyridinyl)-4-pyrimidinyl]amino}methyl)phenyl]methanesulfonamide
- CAS Number: 1621175-65-2
- Molecular Formula: C18H19ClN6O2S
- Molecular Weight: 418.901
- Catalog: Signaling Pathways GPCR/G Protein GHSR
- Create Date: 2018-01-28 20:09:01
- Modify Date: 2024-01-12 01:07:48
-
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.
| Name | N-[3-Chloro-4-({[2-(methylamino)-6-(2-pyridinyl)-4-pyrimidinyl]amino}methyl)phenyl]methanesulfonamide |
|---|---|
| Synonyms |
Methanesulfonamide, N-[3-chloro-4-[[[2-(methylamino)-6-(2-pyridinyl)-4-pyrimidinyl]amino]methyl]phenyl]-
N-[3-Chloro-4-({[2-(methylamino)-6-(2-pyridinyl)-4-pyrimidinyl]amino}methyl)phenyl]methanesulfonamide GPR39-C3 TC-G-1008 |
| Description | 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. |
|---|---|
| Related Catalog | |
| Target |
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]. |
| Kinase Assay | 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 Admin | Mice: Mice are given single oral doses of 10, 30, and 100 mg/kg of TC-G-1008[1]. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 662.1±65.0 °C at 760 mmHg |
| Molecular Formula | C18H19ClN6O2S |
| Molecular Weight | 418.901 |
| Flash Point | 354.2±34.3 °C |
| Exact Mass | 418.097870 |
| LogP | 1.14 |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.678 |
| Storage condition | 2-8℃ |