Dazucorilant (CORT113176) is a non-steroidal glucocorticoid receptor (GR) modulator with an in vitro Ki of <1 nM. Dazucorilant may be utilized in the research of neurological disorders.

Physicochemical Properties

Molecular Formula	C29H22F4N4O3S
Molecular Weight	582.5686
Exact Mass	582.134
CAS #	1496508-34-9
PubChem CID	72192163
Appearance	Off-white to light yellow solid powder
LogP	4.6
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	41
Complexity	1110
Defined Atom Stereocenter Count	1
SMILES	S(C1C([H])=C([H])C(C(F)(F)F)=C([H])C=1[H])(N1C([H])([H])C([H])([H])C2=C([H])C3=C(C([H])=NN3C3C([H])=C([H])C(=C([H])C=3[H])F)C([H])([H])[C@]2(C(C2=C([H])C([H])=C([H])C([H])=N2)=O)C1([H])[H])(=O)=O
InChi Key	VXOBXKQLNWYQPQ-NDEPHWFRSA-N
InChi Code	InChI=1S/C29H22F4N4O3S/c30-22-6-8-23(9-7-22)37-26-15-21-12-14-36(41(39,40)24-10-4-20(5-11-24)29(31,32)33)18-28(21,16-19(26)17-35-37)27(38)25-3-1-2-13-34-25/h1-11,13,15,17H,12,14,16,18H2/t28-/m0/s1
Chemical Name	[(4aR)-1-(4-fluorophenyl)-6-[4-(trifluoromethyl)phenyl]sulfonyl-4,5,7,8-tetrahydropyrazolo[3,4-g]isoquinolin-4a-yl]-pyridin-2-ylmethanone
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	GR[1]
ln Vitro	Dazucorilant functions as a complete antagonist in human hepatocytes or HepG2 human cells since it can both provide non-measurable agonist activity in the absence of dexamethasone and stop the rise in TAT activity brought on by dexamethasone[3].
ln Vivo	Dazucorilant (30 mg/kg/day; SC) causes mice to exhibit glial reactivity, down-regulated proinflammatory mediators, and motoneurons with abnormalities reversed[1]. At a dose of 10 mg/kg, dazucorilant (5, 10 or 20 mg/kg; ip) improves cognitive function by reversing the production of amyloid-β peptides in the hippocampus, as well as neuroinflammation and apoptotic processes. It also restores the levels of synaptic markers in the hippocampus and baseline plasma levels of glucocorticoids.
Animal Protocol	Animal/Disease Models: Wobbler mice (five-month-old)[1] Doses: 30 mg/kg/day Route of Administration: Sc Experimental Results: Wobbler mice demonstrated reversed abnormalities of motoneurons and down-regulated proinflammatory mediators and glial reactivity. Animal/Disease Models: Adult SD male rats[2] Doses: 5, 10 or 20 mg /kg Route of Administration: Ip Experimental Results: Reversed hippocampal amyloid-β peptide generation, neuroinflammation and apoptotic processes, restored the hippocampal levels of synaptic markers, reestablished basal plasma levels of glucocorticoids and improved cognitive function at a dose of 10 mg/kg.
References	[1]. The Selective Glucocorticoid Receptor Modulator Cort 113176 Reduces Neurodegeneration and Neuroinflammation in Wobbler Mice Spinal Cord. Neuroscience. 2018;384:384-396. [2]. New selective glucocorticoid receptor modulators reverse amyloid-β peptide-induced hippocampus toxicity. Neurobiol Aging. 2016;45:109-122. [3]. Central Role of Glucocorticoid Receptors in Alzheimer's Disease and Depression. Front Neurosci. 2018;12:739. Published 2018 Oct 16.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	1.7165 mL	8.5827 mL	17.1653 mL
	5 mM	0.3433 mL	1.7165 mL	3.4331 mL
	10 mM	0.1717 mL	0.8583 mL	1.7165 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.