DREADD agonist 21 (Compound 21) dihydrochloride (water soluble) [HB6124]_Hello Bio - 코아사이언스

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DREADD agonist 21 (Compound 21) dihydrochloride (water soluble) 

Cat.# HB6124 / Size: 5mg, 10mg, 25mg, 100mg

 

Product Overview 

• Name
  DREADD agonist 21 (Compound 21) dihydrochloride (water soluble)
• Short description
  Effective agonist for muscarinic-based DREADDs in vitro and in vivo. Non-CNO chemogenetic actuator. Brain penetrant. Water soluble.
• Biological description

  Overview

  DREADD agonist 21 (Compound 21) hydrochloride is a water soluble salt of DREADD agonist 21 (Compound 21)  which represents an alternative chemogenetic actuator for muscarinic -based DREADDs and an alternative to CNO for in vivo studies in which metabolic conversion of CNO to clozapine is an issue.

  
  DREADD agonist 21 (Compound 21) has excellent bioavailability, pharmacokinetic properties and brain penetrability. It has been reported that the compound does not undergo back metabolism to clozapine.

  
  DREADD agonist 21 is a potent and selective agonist at muscarinic based DREADDs such as the excitatory hM3Dq, hM1Dq and inhibitory hM4Di DREADDs (pEC50 values are 8.48, 8.91 and 7.77 at hM3Dq, hM1Dq and hM4Di respectively). The compound exhibits >10-fold higher affinity at hM1Dq and hM4Di DREADDs compared to wild type receptors and also lacks agonist activity at wild type receptors.

  
  In vivo use

  DREADD agonist 21 from Hello Bio has recently been cited in a pharmacokinetic profile of the compound in mice by Jendryka et al (2019) which suggests that DREADD agonist 21 shows superior brain penetration and long-lasting presence. They suggest that the compound is a suitable DREADD agonist which is effective at latest 15 min after i.p injection, but requires between-subject controls for unspecific effects.

  
  DREADD agonist 21 (Compound 21)-induced activation of hM3Dq and hM4Di can modulate bi-directional feeding in defined circuits in mice. Concentrations of DREADD agonist 21 that resulted in changes in feeding behavior in animals expressing muscarinic DREADDs had no off-target effects in control animals (where musarinic DREADDs were not expressed).

  
  Off target binding

  DREADD agonist 21 shows weak to moderate binding affinity at a range of wild type GPCRs which may translate to functional antagonism in vivo.

  Therefore care should be taken with in vivo dosing of DREADD agonist 21 to ensure the free concentration of the compound remains in a range that activates muscarinic DREADDs but is sufficiently low to avoid antagonism at wild type GPCRs.

  
  Strong competitive binding of DREADD agonist 21 (Cmpd-21) to receptor sites of dopamine, 5-HT, opioid, muscarinic, histamine and adrenoceptors in mice has been shown. Only very subtle, if any behavioural alterations using the 5-CSRTT assessment were found Jendryka et al (2019).

  
  In vivo experiments should be conducted with the appropriate controls where DREADD agonist 21 is administered to animals that do not express the muscarinic-DREADDs.

  
  Data from a poster presented at SfN by the Michaelides group indicates that DREADD agonist 21 (Compound 21) has lower binding affinity for DREADDs compared to clozapine and that DREADD agonist 21 induces behavioural effects in transgenic mice. 1mg/kg doses were used. High doses (10mg/kg) may cause sedation.

• Alternative names
  C21
• Purity
  >98%

Figure: In vivo pharmacokinetic profile of DREADD agonist 21 (Cmpd-21). DREADD agonist 21 was from Hello Bio.

(j–l): Concentration (nM) of Cmpd-21 (blue) at 15, 30 and 60 min after i.p. injection of 3.0 mg/kg Cmpd-21 in (j) plasma, (k) CSF, and (l) cortical brain tissue. Reproduced from Jendryka et al Sci Rep. 2019;9(1):4522

 

Properties 

• Chemical name
  11-(1-Piperazinyl)-5H-dibenzo[b,e][1,4]diazepine dihydrochloride
• Molecular Weight
  352.29
• Chemical structure

  

• Molecular Formula
  C17H18N4.2HCl
• PubChem identifier
  0
• SMILES
  C1CN(CCN1)C2=NC3=CC=CC=C3NC4=CC=CC=C42.Cl.Cl
• Source
  Synthetic
• 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
• Appearance
  Yellow solid

 

Storage & use 

Storage instructions: -20°C

Solubility overview: Soluble in water (100mM). Always store solutions at -20°C.

Handling :

Storage of solid

Store at -20°C.

Please note that the compound is a hydroscopic solid and contact with air may cause material to become sticky. Product performance should not be affected but we recommend storing the material in a sealed jar.

Storage of solutions

Make up solutions and use immediately.

If storage of solutions is required, you should aliquot out the solution into tightly sealed vials and store at -20°C and store these for up to one month.

Allow the product to equilibrate to RT for at least one hour before opening and using.

Handling continued..

Storage of solutions at room temperature

We recommend only keeping solutions at room temperature (25°C) for a few days as our studies have shown that after 96 hours the purity of the compound in solution drops to ~95% and will continue to drop over time.

 

 *본 상품은 오직 연구용으로만 사용 가능합니다. 인체 및 제품화에 사용하실 수 없습니다.

 

References 

The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs. Chen et al (2015) ACS Chem Neurosci 6(3) : 476-84 PubMedID: 25587888

Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits. Spangler and Bruchas (2017) Curr Opin Pharmacol 32(4) : 56-70. PubMedID: 27875804

Clozapine N-Oxide Administration Produces Behavioral Effects in Long-Evans Rats: Implications for Designing DREADD Experiments. MacLaren et al (2016) eNeuro 3(5) : 0219-16 PubMedID: 27822508

Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice. Jendryka et al (2019) Sci Rep. 9(1) : 4522 PubMedID: 30872749

Citations 

Astrocytes Integrate Behavioral State and Vascular Signals during Functional Hyperemia. Tran et al (2018) Neuron doi: : https://doi.org/10.1016/j.neuron

Convergent inputs from the hippocampus and thalamus to the nucleus accumbens regulate dopamine neuron activity. Perez and Lodge(2018) J Neurosci : 2629-16

Olanzapine: a full and potent agonist at the hM4D(Gi) DREADD amenable to clinical translation of chemogenetics. Weston et al (2018) bioRxiv doi: : https://doi.org/10.1101/477513

Microbiota imprint gut–intrinsic neuronal programming and sympathetic activity. Muller and Mucida(2019) bioRxiv : https://www.biorxiv.org/content/

Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice. Jendryka et al (2019) Sci Rep. 9(1) : 4522 PubMedID: 30872749

Olanzapine: A potent agonist at the hM4D(Gi) DREADD amenable to clinical translation of chemogenetics. Weston M et al(2019) Sci Adv 5(4) : 1567 PubMedID: 31001591

 

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