GTS-21 HCl
new
featured

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

MedKoo CAT#: 522507

CAS#: 156223-05-1 (HCl)

Description: GTS-21, also known as DMBX-A, is a derivative of the natural product anabaseine that acts as a partial agonist at neural nicotinic acetylcholine receptors. It binds to both the α4β2 and α7 subtypes, but activates only the α7 to any significant extent. Both GTS-21 itself and its demethylated active metabolite 4-OH-GTS-21 display nootropic and neuroprotective effects, and GTS-21 is being investigated for the treatment of Alzheimer's disease, nicotine dependence, and, most significantly, for schizophrenia.


Chemical Structure

img
GTS-21 HCl
CAS# 156223-05-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 522507
Name: GTS-21 HCl
CAS#: 156223-05-1 (HCl)
Chemical Formula: C19H22Cl2N2O2
Exact Mass: 308.15
Molecular Weight: 381.300
Elemental Analysis: C, 59.85; H, 5.82; Cl, 18.59; N, 7.35; O, 8.39

Price and Availability

Size Price Availability Quantity
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 850 Ready to ship
1g USD 1450 Ready to ship
2g USD 2050 Ready to ship
Bulk inquiry

Related CAS #: 148372-04-7 (free base)   156223-05-1 (HCl)    

Synonym: GTS-21 HCl; GTS-21 hydrochloride; GTS-21; GTS 21; GTS21; DMBX-A

IUPAC/Chemical Name: 3-[(3E)-3-[(2,4-dimethoxyphenyl)methylidene]-5,6-dihydro-4H-pyridin-2-yl]pyridine dihydrochloride

InChi Key: BXKYFUGAAFLYJL-BXGYHSFXSA-N

InChi Code: InChI=1S/C19H20N2O2.2ClH/c1-22-17-8-7-14(18(12-17)23-2)11-15-5-4-10-21-19(15)16-6-3-9-20-13-16;;/h3,6-9,11-13H,4-5,10H2,1-2H3;2*1H/b15-11+;;

SMILES Code: COC1=CC=C(/C=C2C(C3=CC=CN=C3)=NCCC/2)C(OC)=C1.[H]Cl.[H]Cl

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, not in water

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:

Biological target: GTS-21 dihydrochloride is an alpha7 nicotinic acetylcholine receptor (α7-nAChR) agonist.
In vitro activity: Whether GTS-induced alpha7 nAChR can alleviate ischemia-reperfusion-induced intestinal injury was investigated using intestinal epithelial cells (IEC-6). Results showed that the expression of TNF-alpha, IL-1ß, and IL-6 was enhanced when the IEC-6 cells were cultured under OGD/R (oxygen glucose deprivation/reoxygenation) conditions. However, after treatment with GTS-21, the levels of these proinflammatory factors were suppressed. In addition, the levels of ROS and MDA were also inhibited and the expression of SOD was promoted after GTS-21 treatment. The ratios of apoptotic cells also declined after GTS-21 treatment. Reference: Med Sci Monit. 2020 May 17;26:e921618. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251968/
In vivo activity: Whether the nicotinic acetylcholine receptor subtype‑7 (α7‑nAChR) agonist GTS‑21 has a protective effect against RILI (radiation-induced lung injury) was evaluated. C57BL6 mice were irradiated with 12 Gy to induce a mouse model of RILI. Some of the mice received an i.p. injection of 4 mg/kg GTS‑21 for three days with or without radiation treatment. The results showed that GTS‑21 treatment significantly relieved RILI by decreasing TNF‑α, IL‑1β and IL‑6 production in serum via inhibition of NF‑κB activation and downregulation of TLR‑4 and HMGB1 expression in the lungs. In addition, GTS‑21 inhibited NOX‑1 and NOX‑2 expression, which subsequently reduced ROS levels and Hif‑1α expression in RILI. However, GTS‑21 showed little effect on lung tissue without radiation exposure. The protective effect of GTS‑21 against RILI is partly attributed to inhibition of the HMGB1/TLR4/NF‑κB pathway and ROS production. Reference: Oncol Rep. 2018 Oct;40(4):2287-2297. https://www.spandidos-publications.com/or/40/4/2287

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Water 50.0 131.13
DMSO 12.5 32.84
DMF 1.0 2.62
Ethanol 1.0 2.62
PBS (pH 7.2) 10.0 26.23

Preparing Stock Solutions

The following data is based on the product molecular weight 381.30 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.

Recalculate based on batch purity %
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. Wang H, Cai D, Chen Z, Wang Y. GTS-21 Promotes α7 nAChR to Alleviate Intestinal Ischemia-Reperfusion-Induced Apoptosis and Inflammation of Enterocytes. Med Sci Monit. 2020 May 17;26:e921618. doi: 10.12659/MSM.921618. PMID: 32417847; PMCID: PMC7251968. 2. Mei Z, Tian X, Chen J, Wang Y, Yao Y, Li X, Yang C, Zhang S, Xie C. α7‑nAchR agonist GTS‑21 reduces radiation‑induced lung injury. Oncol Rep. 2018 Oct;40(4):2287-2297. doi: 10.3892/or.2018.6616. Epub 2018 Aug 1. PMID: 30106431. 3. Kong W, Kang K, Gao Y, Liu H, Meng X, Cao Y, Yang S, Liu W, Zhang J, Yu K, Zhao M. GTS-21 Protected Against LPS-Induced Sepsis Myocardial Injury in Mice Through α7nAChR. Inflammation. 2018 Jun;41(3):1073-1083. doi: 10.1007/s10753-018-0759-x. PMID: 29680908.
In vitro protocol: 1. Wang H, Cai D, Chen Z, Wang Y. GTS-21 Promotes α7 nAChR to Alleviate Intestinal Ischemia-Reperfusion-Induced Apoptosis and Inflammation of Enterocytes. Med Sci Monit. 2020 May 17;26:e921618. doi: 10.12659/MSM.921618. PMID: 32417847; PMCID: PMC7251968.
In vivo protocol: 1. Mei Z, Tian X, Chen J, Wang Y, Yao Y, Li X, Yang C, Zhang S, Xie C. α7‑nAchR agonist GTS‑21 reduces radiation‑induced lung injury. Oncol Rep. 2018 Oct;40(4):2287-2297. doi: 10.3892/or.2018.6616. Epub 2018 Aug 1. PMID: 30106431. 2. Kong W, Kang K, Gao Y, Liu H, Meng X, Cao Y, Yang S, Liu W, Zhang J, Yu K, Zhao M. GTS-21 Protected Against LPS-Induced Sepsis Myocardial Injury in Mice Through α7nAChR. Inflammation. 2018 Jun;41(3):1073-1083. doi: 10.1007/s10753-018-0759-x. PMID: 29680908.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Yue Y, Liu R, Cheng W, Hu Y, Li J, Pan X, Peng J, Zhang P. GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor. Int Immunopharmacol. 2015 Oct 17. pii: S1567-5769(15)30138-7. doi: 10.1016/j.intimp.2015.10.005. [Epub ahead of print] PubMed PMID: 26490221.

2: Kong FJ, Ma LL, Zhang HH, Zhou JQ. Alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigates isoflurane-induced cognitive impairment in aged rats. J Surg Res. 2015 Mar;194(1):255-61. doi: 10.1016/j.jss.2014.09.043. Epub 2014 Oct 5. PubMed PMID: 25450597.

3: Wu S, Zhao H, Luo H, Xiao X, Zhang H, Li T, Zuo X. GTS-21, an α7-nicotinic acetylcholine receptor agonist, modulates Th1 differentiation in CD4(+) T cells from patients with rheumatoid arthritis. Exp Ther Med. 2014 Aug;8(2):557-562. Epub 2014 Jun 3. PubMed PMID: 25009619; PubMed Central PMCID: PMC4079428.

4: Hu Y, Liu R, Li J, Yue Y, Cheng W, Zhang P. Attenuation of Collagen-Induced Arthritis in rat by nicotinic alpha7 receptor partial agonist GTS-21. Biomed Res Int. 2014;2014:325875. doi: 10.1155/2014/325875. Epub 2014 Feb 27. PubMed PMID: 24719855; PubMed Central PMCID: PMC3955649.

5: Sitapara RA, Antoine DJ, Sharma L, Patel VS, Ashby CR Jr, Gorasiya S, Yang H, Zur M, Mantell LL. The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function. Mol Med. 2014 Jun 19;20:238-47. doi: 10.2119/molmed.2013.00086. PubMed PMID: 24664237; PubMed Central PMCID: PMC4069272.

6: Callahan PM, Terry AV Jr, Tehim A. Effects of the nicotinic α7 receptor partial agonist GTS-21 on NMDA-glutamatergic receptor related deficits in sensorimotor gating and recognition memory in rats. Psychopharmacology (Berl). 2014 Sep;231(18):3695-706. doi: 10.1007/s00213-014-3509-2. Epub 2014 Mar 5. PubMed PMID: 24595504.

7: Thomsen MS, Mikkelsen JD. The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia. J Neuroimmunol. 2012 Oct 15;251(1-2):65-72. doi: 10.1016/j.jneuroim.2012.07.006. Epub 2012 Aug 9. PubMed PMID: 22884467.

8: Khan MA, Farkhondeh M, Crombie J, Jacobson L, Kaneki M, Martyn JA. Lipopolysaccharide upregulates α7 acetylcholine receptors: stimulation with GTS-21 mitigates growth arrest of macrophages and improves survival in burned mice. Shock. 2012 Aug;38(2):213-9. doi: 10.1097/SHK.0b013e31825d628c. PubMed PMID: 22683726; PubMed Central PMCID: PMC3399057.

9: Cannon CE, Puri V, Vivian JA, Egbertson MS, Eddins D, Uslaner JM. The nicotinic α7 receptor agonist GTS-21 improves cognitive performance in ketamine impaired rhesus monkeys. Neuropharmacology. 2013 Jan;64:191-6. doi: 10.1016/j.neuropharm.2012.05.003. Epub 2012 May 29. PubMed PMID: 22659472.

10: Kox M, Pompe JC, Peters E, Vaneker M, van der Laak JW, van der Hoeven JG, Scheffer GJ, Hoedemaekers CW, Pickkers P. α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced tumour necrosis factor-α production and lung injury. Br J Anaesth. 2011 Oct;107(4):559-66. doi: 10.1093/bja/aer202. Epub 2011 Jul 18. PubMed PMID: 21771746.

11: Kox M, Pompe JC, Gordinou de Gouberville MC, van der Hoeven JG, Hoedemaekers CW, Pickkers P. Effects of the α7 nicotinic acetylcholine receptor agonist GTS-21 on the innate immune response in humans. Shock. 2011 Jul;36(1):5-11. doi: 10.1097/SHK.0b013e3182168d56. PubMed PMID: 21368716.

12: Chen L, Wang H, Zhang Z, Li Z, He D, Sokabe M, Chen L. DMXB (GTS-21) ameliorates the cognitive deficits in beta amyloid(25-35(-) ) injected mice through preventing the dysfunction of alpha7 nicotinic receptor. J Neurosci Res. 2010 Jun;88(8):1784-94. doi: 10.1002/jnr.22345. PubMed PMID: 20127813.

13: López-Hernández GY, Thinschmidt JS, Morain P, Trocme-Thibierge C, Kem WR, Soti F, Papke RL. Positive modulation of alpha7 nAChR responses in rat hippocampal interneurons to full agonists and the alpha7-selective partial agonists, 4OH-GTS-21 and S 24795. Neuropharmacology. 2009 Mar;56(4):821-30. PubMed PMID: 19705574; PubMed Central PMCID: PMC2775526.

14: Rosas-Ballina M, Goldstein RS, Gallowitsch-Puerta M, Yang L, Valdés-Ferrer SI, Patel NB, Chavan S, Al-Abed Y, Yang H, Tracey KJ. The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE. Mol Med. 2009 Jul-Aug;15(7-8):195-202. doi: 10.2119/molmed.2009.00039. Epub 2009 Apr 27. PubMed PMID: 19593403; PubMed Central PMCID: PMC2707516.

15: Kox M, van Velzen JF, Pompe JC, Hoedemaekers CW, van der Hoeven JG, Pickkers P. GTS-21 inhibits pro-inflammatory cytokine release independent of the Toll-like receptor stimulated via a transcriptional mechanism involving JAK2 activation. Biochem Pharmacol. 2009 Oct 1;78(7):863-72. doi: 10.1016/j.bcp.2009.06.096. Epub 2009 Jul 1. PubMed PMID: 19576181.

16: Thinschmidt JS, López-Hernández GY, Ren K, King MA, Meyer EM, Papke RL. Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated alpha7 nicotinic receptor gene transfer. Brain Res. 2008 Apr 8;1203:51-60. doi: 10.1016/j.brainres.2008.02.011. Epub 2008 Feb 14. PubMed PMID: 18321476; PubMed Central PMCID: PMC2577826.

17: Ren K, King MA, Liu J, Siemann J, Altman M, Meyers C, Hughes JA, Meyer EM. The alpha7 nicotinic receptor agonist 4OH-GTS-21 protects axotomized septohippocampal cholinergic neurons in wild type but not amyloid-overexpressing transgenic mice. Neuroscience. 2007 Aug 10;148(1):230-7. Epub 2007 Jul 20. PubMed PMID: 17640819.

18: Kim SW, Ding YS, Alexoff D, Patel V, Logan J, Lin KS, Shea C, Muench L, Xu Y, Carter P, King P, Constanzo JR, Ciaccio JA, Fowler JS. Synthesis and positron emission tomography studies of C-11-labeled isotopomers and metabolites of GTS-21, a partial alpha7 nicotinic cholinergic agonist drug. Nucl Med Biol. 2007 Jul;34(5):541-51. PubMed PMID: 17591554; PubMed Central PMCID: PMC3182824.

19: Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish WR, Rosas-Ballina M, Czura CJ, Larosa GJ, Miller EJ, Tracey KJ, Al-Abed Y. Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med. 2007 Apr;35(4):1139-44. PubMed PMID: 17334244.

20: Wei DQ, Sirois S, Du QS, Arias HR, Chou KC. Theoretical studies of Alzheimer's disease drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine (GTS-21) and its derivatives. Biochem Biophys Res Commun. 2005 Dec 16;338(2):1059-64. Epub 2005 Oct 21. PubMed PMID: 16256952.