JHU37152 is a potent and BBB (blood-brain barrier) permeable (penetrable) DREADD agonist/activator with EC50s of 5 nM and 0.5 nM for hM3Dq and hM4Di DREADDs, respectively. JHU37152 displays selective [3H]Clozapine displacement from DREADDs but not from other Clozapine binding sites in mouse brain tissue.

Physicochemical Properties

Molecular Formula	C19H20CLFN4
Molecular Weight	358.8403
Exact Mass	358.136
CAS #	2369979-67-7
PubChem CID	139033721
Appearance	White to yellow solid powder
LogP	3.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	25
Complexity	494
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C([H])C2=C(C=1[H])N=C(C1C(=C([H])C([H])=C([H])C=1N2[H])F)N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1([H])[H]
InChi Key	NZMZJNNWMSYDNX-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H20ClFN4/c1-2-24-8-10-25(11-9-24)19-18-14(21)4-3-5-16(18)22-15-7-6-13(20)12-17(15)23-19/h3-7,12,22H,2,8-11H2,1H3
Chemical Name	3-chloro-6-(4-ethylpiperazin-1-yl)-7-fluoro-11H-benzo[b][1,4]benzodiazepine
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	EC50: 5 nM (hM3Dq DREADD); 0.5 nM (hM4Di DREADD)[1]
ln Vitro	With Kis of 1.8 nM and 8.7 nM for hM3Dq and hM4Di expressed in mouse brain slices, respectively, JHU37152 exhibits strong DREADD affinity[1]. [3H]Clozapine displacement from DREADDs is selectively displaced by JHU37152 (1-1000 nM), but not from other Clozapine-binding sites[1].
ln Vivo	In mice and rats, JHU37152 (0.1 mg/kg; ip) shows strong DREADD occupancy[1]. Without significantly affecting WT mice's locomotor activity, JHU37152 (0.01–1 mg/kg; ip) specifically suppresses locomotor activity in D1–hM3Dq and D1–hM4Di mice[1].
References	[1]. High-potency ligands for DREADD imaging and activation in rodents and monkeys. Nat Commun. 2019 Oct 11;10(1):4627.

Solubility Data

Solubility (In Vitro)

DMSO: 33.33 mg/mL (92.88 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7868 mL	13.9338 mL	27.8676 mL
	5 mM	0.5574 mL	2.7868 mL	5.5735 mL
	10 mM	0.2787 mL	1.3934 mL	2.7868 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.