| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
GPR39 ( IC50 = 0.4 nM ); GPR39 ( IC50 = 0.8 nM )
TC-G-1008 targets GPR39, a G protein-coupled receptor that is activated by zinc ions and is involved in metabolism, gastrointestinal function, and neuroprotection. By activating GPR39, TC-G-1008 induces acute GLP-1 levels and has potential applications in metabolic disorders. The compound shows selectivity over ghrelin and neurotensin-1 receptors. |
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| ln Vitro |
TC-G-1008 demonstrates selectivity towards a range of kinases (IC50s>10 μM) and lacks significant binding affinity towards the associated ghrelin and neurotensin-1 receptors (IC50s>30 μM)[1]. GPR39-C3, a positive allosteric modulator, stimulates the production of cAMP (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment in HEK293-GPR39 cells. By introducing the compound again, GPR39-C3 causes a dose- and time-dependent loss of response in the synthesis of cAMP[2].
In vitro, TC-G-1008 is a potent GPR39 agonist with EC50 values of 0.4 nM for rat and 0.8 nM for human receptors. It is the first potent GPR39 agonist with EC50s ≤ 1 nM for human and rat receptors. The compound shows selectivity over ghrelin and neurotensin-1 receptors with IC50s > 10 μM and > 30 μM, respectively. |
| ln Vivo |
For TC-G-1008, the measured levels of rat and mouse plasma protein binding are 99.3% and 99.1%, respectively. In mice, TC-G-1008 is orally bioavailable and effectively raises acute GLP-1 levels. After taking 10, 30, and 100 mg/kg of aqueous suspensions in 0.5% methylcellulose/0.1% Tween 80 orally, TC-G-1008 reaches maximal exposures of 1.4, 6.1, and 25.3 μM in 1 to 1.5 hours, respectively[1].
In vivo, TC-G-1008 is orally bioavailable in mice and robustly induces acute GLP-1 levels upon single oral doses of 10 mg/kg. The compound shows high plasma protein binding in rats (99.3%) and mice (99.1%). Its ability to induce GLP-1 secretion makes it a promising tool for studying GPR39 function in metabolism. |
| Enzyme Assay |
HEK293-GPR39 cells are plated and grown in the growth medium for an entire night at 37°C with 5% CO2 in white, 384-well plates coated with poly-d-lysine (4000 cells/well). The culture medium is removed before the cells are stimulated with GPR39 ligands in assay buffer for the specified amount of time at 37°C. This is done for pretreatment of the cells with GPR39 ligands (TC-G-1008) or vehicle control (DMSO). After that, the compound solution is taken out and twice cleaned using PBS that has 0.1% BSA added. The cells are stimulated with drugs in stimulation buffer for 30 minutes at 37°C in order to measure the amount of intracellular cAMP. The HTRF cAMP dynamic 2 kit is used to measure the intracellular cAMP level[2].
In vitro receptor binding assays for TC-G-1008 measure its affinity for GPR39 using functional assays. Cells expressing rat or human GPR39 are treated with serial dilutions of the compound, and receptor activation is measured by assessing downstream signaling such as cAMP accumulation or calcium mobilization. EC50 values of 0.4 nM and 0.8 nM are determined for rat and human receptors, respectively. |
| Cell Assay |
In vitro cell-based assays for TC-G-1008 use cells expressing rat or human GPR39. Cells are treated with serial dilutions of the compound, and receptor activation is measured by cAMP accumulation or other signaling readouts. EC50 values are calculated from dose-response curves. Selectivity is confirmed by testing against ghrelin and neurotensin-1 receptors.
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| Animal Protocol |
Mice: Single oral doses of TC-G-1008 at 10, 30, and 100 mg/kg are administered to mice[1].
In vivo animal models for TC-G-1008 include mouse models of metabolic disorders. The compound is administered orally, and its effects on plasma GLP-1 levels and glucose metabolism are evaluated. Pharmacodynamic studies measure GPR39 activation and GLP-1 secretion in response to compound treatment. The compound's oral bioavailability has been demonstrated in mice. |
| ADME/Pharmacokinetics |
TC-G-1008 has a molecular formula of C18H19ClN6O2S and a molecular weight of 418.9 g/mol. It is stored as a powder at -20°C for up to 3 years and has a purity of >98%. The compound is also known as GPR39-C3 and is orally bioavailable.
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| Toxicity/Toxicokinetics |
The toxicity profile of TC-G-1008 is characterized in preclinical safety studies. As a GPR39 agonist, the compound may affect metabolism and gastrointestinal function. The compound is for research use only and is not approved for clinical use. Appropriate safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
TC-G-1008 (GPR39-C3) is a potent and orally bioavailable GPR39 agonist with EC50 values of 0.4 nM and 0.8 nM for rat and human receptors, respectively. It is the first potent GPR39 agonist (EC50s ≤ 1 nM) that is orally bioavailable in mice and robustly induces acute GLP-1 levels. The compound shows high plasma protein binding (99.3% in rats, 99.1% in mice) and is intended for laboratory research use only.
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| Molecular Formula |
C18H19CLN6O2S
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|---|---|
| Molecular Weight |
418.9
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| Exact Mass |
418.097
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| Elemental Analysis |
C, 51.61; H, 4.57; Cl, 8.46; N, 20.06; O, 7.64; S, 7.65
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| CAS # |
1621175-65-2
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| Related CAS # |
1621175-65-2
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| PubChem CID |
91826086
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
662.1±65.0 °C at 760 mmHg
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| Flash Point |
354.2±34.3 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.678
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| LogP |
1.14
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
589
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])N([H])C1C([H])=C(C2=C([H])C([H])=C([H])C([H])=N2)N=C(N([H])C([H])([H])[H])N=1)N([H])S(C([H])([H])[H])(=O)=O
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| InChi Key |
DRSZMILOMUPIBJ-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
N-[3-chloro-4-[[[2-(methylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide
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| Synonyms |
GPR39-C3; GPR39C3; GPR39 C3; TC-G-1008; TC-G1008; TC-G 1008; TCG-1008; TCG1008; TCG 1008
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~84 mg/mL (~200.5 mM)
Ethanol: ~2 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3872 mL | 11.9360 mL | 23.8720 mL | |
| 5 mM | 0.4774 mL | 2.3872 mL | 4.7744 mL | |
| 10 mM | 0.2387 mL | 1.1936 mL | 2.3872 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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