TC-G-1008 | GPR39-C3 | CAS#1621175-65-2 | GPR39 Agonist

MedKoo Cat#: 530321 | Name: TC-G-1008

Description:

WARNING: This product is for research use only, not for human or veterinary use.

TC-G-1008, also known as GPR39-C3, is a potent and selective agonist of the G-protein-coupled receptor 39 (GPR39), exhibiting EC₅₀ values of 0.4 nM and 0.8 nM for rat and human receptors, respectively. It has demonstrated various bioactivities across multiple studies. In human fibroblast-like synoviocytes, TC-G 1008 reduced tumor necrosis factor-alpha (TNF-α)-induced oxidative stress, mitochondrial dysfunction, cytokine expression, and secretion of matrix metalloproteinases. In a mouse model of intracerebral hemorrhage, it promoted mitochondrial biogenesis and enhanced antioxidative capacity via the CREB/PGC-1α pathway. TC-G 1008 exhibits beneficial anti-inflammatory and neuroprotective properties.

Chemical Structure

TC-G-1008

CAS#1621175-65-2

Theoretical Analysis

MedKoo Cat#: 530321

Name: TC-G-1008

CAS#: 1621175-65-2

Chemical Formula: C18H19ClN6O2S

Exact Mass: 418.0979

Molecular Weight: 418.90

Elemental Analysis: C, 51.61; H, 4.57; Cl, 8.46; N, 20.06; O, 7.64; S, 7.65

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,850.00	Ready to ship

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Synonym

GPR39-C3, GPR39C3, GPR39 C3, TC-G-1008, TC-G1008, TC-G 1008, TCG-1008, TCG1008, TCG 1008

IUPAC/Chemical Name

N-[3-Chloro-4-[[[2-(methylamino)-6-(2-pyridinyl)-4-pyrimidinyl]amino]methyl]phenyl]methanesulfonamide

InChi Key

DRSZMILOMUPIBJ-UHFFFAOYSA-N

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)

SMILES Code

CS(=O)(NC1=CC=C(CNC2=NC(NC)=NC(C3=NC=CC=C3)=C2)C(Cl)=C1)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A22T12K05

QC Data

View QC data: current batch, Lot#A22T12K05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

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.

In vitro activity:

In HEK293-GPR39 cells, GPR39-C3, which is a positive allosteric modulator, activated cAMP production (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment. GPR39-C3 induced dose- and time-dependent loss of response in cAMP production by second challenge of the compound. Reference: Biochem Pharmacol. 2017 Sep 15;140:105-114. https://pubmed.ncbi.nlm.nih.gov/28619258/

In vivo activity:

This study also tested the effects of a GPR39 agonist (TC-G 1008) on declarative memory of old animals, and its disruption in adult mice. This study observed episodic-like memory (ELM) and spatial memory (SM) deficits in male GPR39 KO mice, as well as intact procedural memory in GPR39 KO mice regardless of age and sex. Reference: Neuroscience. 2022 Nov 1;503:1-16. https://pubmed.ncbi.nlm.nih.gov/36087899/

	Solvent	mg/mL	mM
Solubility
	DMSO	64.0	152.72
	DMSO:PBS (pH 7.2) (1:5)	0.2	0.38
	Ethanol	2.0	4.77

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 418.90 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Meda Venkata SP, Li H, Xu L, Koh JY, Nguyen H, Minjares M, Li C, Kowluru A, Milligan G, Wang JM. Inhibition of GPR39 restores defects in endothelial cell-mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis. Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2208541120. doi: 10.1073/pnas.2208541120. Epub 2022 Dec 27. PMID: 36574661. 2. Shimizu Y, Koyama R, Kawamoto T. Rho kinase-dependent desensitization of GPR39; a unique mechanism of GPCR downregulation. Biochem Pharmacol. 2017 Sep 15;140:105-114. doi: 10.1016/j.bcp.2017.06.115. Epub 2017 Jun 12. PMID: 28619258. 3. Rychlik M, Starowicz G, Starnowska-Sokol J, Mlyniec K. The Zinc-sensing Receptor (GPR39) Modulates Declarative Memory and Age-related Hippocampal Gene Expression in Male Mice. Neuroscience. 2022 Nov 1;503:1-16. doi: 10.1016/j.neuroscience.2022.09.002. Epub 2022 Sep 7. PMID: 36087899. 4. Xie S, Jiang X, Doycheva DM, Shi H, Jin P, Gao L, Liu R, Xiao J, Hu X, Tang J, Zhang L, Zhang JH. Activation of GPR39 with TC-G 1008 attenuates neuroinflammation via SIRT1/PGC-1α/Nrf2 pathway post-neonatal hypoxic-ischemic injury in rats. J Neuroinflammation. 2021 Oct 13;18(1):226. doi: 10.1186/s12974-021-02289-7. PMID: 34645465; PMCID: PMC8513331.

In vitro protocol:

In vivo protocol:

1. Rychlik M, Starowicz G, Starnowska-Sokol J, Mlyniec K. The Zinc-sensing Receptor (GPR39) Modulates Declarative Memory and Age-related Hippocampal Gene Expression in Male Mice. Neuroscience. 2022 Nov 1;503:1-16. doi: 10.1016/j.neuroscience.2022.09.002. Epub 2022 Sep 7. PMID: 36087899. 2. Xie S, Jiang X, Doycheva DM, Shi H, Jin P, Gao L, Liu R, Xiao J, Hu X, Tang J, Zhang L, Zhang JH. Activation of GPR39 with TC-G 1008 attenuates neuroinflammation via SIRT1/PGC-1α/Nrf2 pathway post-neonatal hypoxic-ischemic injury in rats. J Neuroinflammation. 2021 Oct 13;18(1):226. doi: 10.1186/s12974-021-02289-7. PMID: 34645465; PMCID: PMC8513331.

1: Sanz-Martinez P, Tascher G, Cano-Franco S, Cabrerizo-Poveda P, Münch C, Homan EJ, Stolz A. GPCR Function in Autophagy Control: A Systematic Approach of Chemical Intervention. J Mol Biol. 2024 Aug 1;436(15):168643. doi: 10.1016/j.jmb.2024.168643. Epub 2024 Jun 5. PMID: 38848865. 2: Zhang Z, Yuan Y, Zhang X, Gu L, Tang Y, Zhao Y, Dai J, Tao Y, Xie Z. GPR39 Agonist TC-G 1008 Promoted Mitochondrial Biogenesis and Improved Antioxidative Capability via CREB/PGC-1α Pathway Following Intracerebral Hemorrhage in Mice. Transl Stroke Res. 2024 Mar 15. doi: 10.1007/s12975-024-01240-1. Epub ahead of print. PMID: 38485864. 3: Doboszewska U, Maret W, Wlaź P. GPR39: An orphan receptor begging for ligands. Drug Discov Today. 2024 Feb;29(2):103861. doi: 10.1016/j.drudis.2023.103861. Epub 2023 Dec 19. PMID: 38122967. 4: Cheng F, Yan F, Yang A, Liu J, Ma J. Activation of G protein-coupled receptor 39 alleviates neuropathic pain and chronic inflammation. J Biochem Mol Toxicol. 2024 Jan;38(1):e23545. doi: 10.1002/jbt.23545. Epub 2023 Oct 16. PMID: 37842769. 5: Zhang L, Tan X, Song F, Li D, Wu J, Gao S, Sun J, Liu D, Zhou Y, Mei W. Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model. Neural Regen Res. 2024 Mar;19(3):687-696. doi: 10.4103/1673-5374.380905. PMID: 37721302; PMCID: PMC10581569. 6: Rychlik M, Starnowska-Sokol J, Mlyniec K. Chronic memantine disrupts spatial memory and up-regulates Htr1a gene expression in the hippocampus of GPR39 (zinc- sensing receptor) KO male mice. Brain Res. 2023 Dec 15;1821:148577. doi: 10.1016/j.brainres.2023.148577. Epub 2023 Sep 14. PMID: 37716463. 7: Doboszewska U, Socała K, Pieróg M, Nieoczym D, Sawicki J, Szafarz M, Gawel K, Rafało-Ulińska A, Sajnóg A, Wyska E, Esguerra CV, Szewczyk B, Maćkowiak M, Barałkiewicz D, Mlyniec K, Nowak G, Sowa I, Wlaź P. TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice. Cell Mol Life Sci. 2023 Apr 25;80(5):133. doi: 10.1007/s00018-023-04766-z. PMID: 37185787; PMCID: PMC10130118. 8: Starowicz G, Siodłak D, Nowak G, Mlyniec K. The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission. Pharmacol Rep. 2023 Jun;75(3):609-622. doi: 10.1007/s43440-023-00478-0. Epub 2023 Mar 30. PMID: 36997827; PMCID: PMC10227137. 9: Doboszewska U, Socała K, Pieróg M, Nieoczym D, Sawicki J, Sajnóg A, Szewczyk B, Mlyniec K, Sowa I, Barałkiewicz D, Wlaź P. Dietary Zinc Differentially Regulates the Effects of the GPR39 Receptor Agonist, TC-G 1008, in the Maximal Electroshock Seizure Test and Pentylenetetrazole-Kindling Model of Epilepsy. Cells. 2023 Jan 9;12(2):264. doi: 10.3390/cells12020264. PMID: 36672199; PMCID: PMC9856893. 10: Meda Venkata SP, Li H, Xu L, Koh JY, Nguyen H, Minjares M, Li C, Kowluru A, Milligan G, Wang JM. Inhibition of GPR39 restores defects in endothelial cell- mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis. Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2208541120. doi: 10.1073/pnas.2208541120. Epub 2022 Dec 27. PMID: 36574661; PMCID: PMC9910611. 11: Rychlik M, Starowicz G, Starnowska-Sokol J, Mlyniec K. The Zinc-sensing Receptor (GPR39) Modulates Declarative Memory and Age-related Hippocampal Gene Expression in Male Mice. Neuroscience. 2022 Nov 1;503:1-16. doi: 10.1016/j.neuroscience.2022.09.002. Epub 2022 Sep 7. PMID: 36087899. 12: Yang P, Feng Q, Meng L, Tang R, Jiang Y, Liu H, Si H, Li M. The mechanism underlying the TC-G 1008 rescue of reactive oxygen species (ROS)-induced osteoblast apoptosis by the upregulation of peroxiredoxin 1. Int J Biochem Cell Biol. 2022 Oct;151:106276. doi: 10.1016/j.biocel.2022.106276. Epub 2022 Aug 8. PMID: 35953014. 13: Doboszewska U, Sawicki J, Sajnóg A, Szopa A, Serefko A, Socała K, Pieróg M, Nieoczym D, Mlyniec K, Nowak G, Barałkiewicz D, Sowa I, Wlaź P. Alterations of Serum Magnesium Concentration in Animal Models of Seizures and Epilepsy-The Effects of Treatment with a GPR39 Agonist and Knockout of the Gpr39 Gene. Cells. 2022 Jun 21;11(13):1987. doi: 10.3390/cells11131987. PMID: 35805072; PMCID: PMC9265460. 14: Xie S, Jiang X, Doycheva DM, Shi H, Jin P, Gao L, Liu R, Xiao J, Hu X, Tang J, Zhang L, Zhang JH. Activation of GPR39 with TC-G 1008 attenuates neuroinflammation via SIRT1/PGC-1α/Nrf2 pathway post-neonatal hypoxic-ischemic injury in rats. J Neuroinflammation. 2021 Oct 13;18(1):226. doi: 10.1186/s12974-021-02289-7. PMID: 34645465; PMCID: PMC8513331. 15: Mo F, Tang Y, Du P, Shen Z, Yang J, Cai M, Zhang Y, Li H, Shen H. GPR39 protects against corticosterone-induced neuronal injury in hippocampal cells through the CREB-BDNF signaling pathway. J Affect Disord. 2020 Jul 1;272:474-484. doi: 10.1016/j.jad.2020.03.137. Epub 2020 Apr 30. PMID: 32553391. 16: Satianrapapong W, Pongkorpsakol P, Muanprasat C. A G-protein coupled receptor 39 agonist stimulates proliferation of keratinocytes via an ERK- dependent pathway. Biomed Pharmacother. 2020 Jul;127:110160. doi: 10.1016/j.biopha.2020.110160. Epub 2020 May 1. PMID: 32371316. 17: Shan W, Qi J, Li C, Nie X. Agonism of GPR39 displays protective effects against advanced glycation end-product (AGE)-induced degradation of extracellular matrix in human SW1353 cells. Arch Biochem Biophys. 2019 Nov 30;677:108164. doi: 10.1016/j.abb.2019.108164. Epub 2019 Oct 31. PMID: 31678046. 18: Jing W, Sun W, Zhang N, Zhao C, Yan X. The protective effects of the GPR39 agonist TC-G 1008 against TNF-α-induced inflammation in human fibroblast-like synoviocytes (FLSs). Eur J Pharmacol. 2019 Dec 15;865:172663. doi: 10.1016/j.ejphar.2019.172663. Epub 2019 Sep 17. PMID: 31539553. 19: Chai X, Zhang W, Chang B, Feng X, Song J, Li L, Yu C, Zhao J, Si H. GPR39 agonist TC-G 1008 promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3569-3576. doi: 10.1080/21691401.2019.1649270. PMID: 31448639. 20: Lu H, Wang D, Li H, Zhong J, Lin Y, Xu X, Wang B. GPR39 agonist TC-G 1008 ameliorates IL-1β-induced chondrocyte senescence. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2612-2617. doi: 10.1080/21691401.2019.1626405. Retraction in: Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):285. doi: 10.1080/21691401.2021.1899416. PMID: 31237151.