DREADD agonist 21 dihydrochloride

• CAT Number: I045900
• CAS Number: 2250025-92-2
• Molecular Formula: C17H20Cl2N4
• Molecular Weight: 351.27
• Purity: ≥95%
• Synonyms: 6-piperazin-1-yl-11H-benzo[b][1,4]benzodiazepine;dihydrochloride
• InChI: InChI=1S/C17H18N4.2ClH/c1-2-6-14-13(5-1)17(21-11-9-18-10-12-21)20-16-8-4-3-7-15(16)19-14;;/h1-8,18-19H,9-12H2;2*1H
• InChIKey: SETCOPAXYQJWKI-UHFFFAOYSA-N
• SMILES: C1CN(CCN1)C2=NC3=CC=CC=C3NC4=CC=CC=C42.Cl.Cl

DREADD agonist 21 dihydrochloride is a potent human muscarinic acetylcholine M3 receptors (hM3Dq) agonist (EC50=1.7 nM)[1].
DREADD agonist 21 is a potent human muscarinic acetylcholine M3 receptors (hM3Dq) agonist (EC50=1.7 nM) and does not activate human M3 receptor (hM3). In addition to being inactive at hM3, DREADD agonist 21, a potent full agonist of hM3Dq (EC50=1.7 nM), is only 3.5-fold selective for hM3Dq over H1, 40-fold selective over 5HT2A, 100-fold selective over 5HT2C, and 165-fold selective over α1A. DREADD agonist 21 shows high binding affinities to 5HT2A and 5HT2C serotonin receptor, α1A adrenergic receptor, and H1 histamine receptor with Ki values of 66, 170, 280, and 6 nM, respectively[1].
DREADD agonist 21 potently activates hM1Dq, hM3Dq, and hM4Di. DREADD agonist 21 binds to hM1, hM4, hM1Dq and hM4Di receptors with pKis of 5.97, 5.44, 7.20, and 6.75, respectively. DREADD agonist 21 potently activates hM3Dq in Chinese hamster ovary (CHO) cells transfected cells in vitro with a pEC50 of 8.48±0.05. DREADD agonist 21 is a highly selective and potent agonist for muscarinic DREADDs (pEC50 for hM1Dq=6.54 and that for hM4Di=7.77 in pERK assays)[2].
DREADD agonist 21 (0.3, 1.0, and 3.0 mg/kg; i.p.) activates neuronal hM3Dq in mice[2].
DREADD agonist 21 has excellent bioavailability, pharmacokinetic properties, and brain penetrability. DREADD agonist 21 (0.1, 1, and 10 mg/kg; i.p.) displays 95.1% plasma protein binding and 95% brain protein bounding in mice[2].

Reference

[1]. Chen X, et al. The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs. ACS Chem Neurosci. 2015 Mar 18;6(3):476-84.
 [Content Brief]

[2]. Thompson KJ, et al. DREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDs in Vitro and in Vivo. ACS Pharmacol Transl Sci. 2018 Sep 14;1(1):61-72.
 [Content Brief]