Nrf2 activator-3 is a potent Nrf2 activator. Nrf2 activator-3 for the study of cerebral ischemic injury.

Physicochemical Properties

Molecular Formula	C23H18F3N3O2
Molecular Weight	425.40313577652
Exact Mass	425.135
CAS #	2766570-23-2
PubChem CID	168285762
Appearance	Off-white to light yellow solid powder
LogP	5.9
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	31
Complexity	597
Defined Atom Stereocenter Count	0
SMILES	FC(C1C=CC(=C(C=1)O)C1N=C(C2C=CC=CC=2O)N(C2C=C(C)C=C(C)C=2)N=1)(F)F
InChi Key	INMUTDNBXNPVRS-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H18F3N3O2/c1-13-9-14(2)11-16(10-13)29-22(18-5-3-4-6-19(18)30)27-21(28-29)17-8-7-15(12-20(17)31)23(24,25)26/h3-12,30-31H,1-2H3
Chemical Name	2-[1-(3,5-dimethylphenyl)-5-(2-hydroxyphenyl)-1,2,4-triazol-3-yl]-5-(trifluoromethyl)phenol
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

ln Vitro	Nrf2 activator-3 (compound 24) reduces SNP (400 μM)-induced cell death in PC12 cells at concentrations of 1 μM, 5 μM, and 10 μM. The IC50 values for these concentrations are 76.86±3.54 μM, 101.59±3.34 μM, and 105.1±1.84 μM, respectively [1]. On PC12 and hacat cells, the IC50 values of Nrf2 activator-3 (1-200 μM) are 262.70±1.98 μM and 126.70±10.39 μM, respectively [1].
ln Vivo	Nrf2 activator-3 (compound 24) exhibited toxicity to experimental mice at 1000 mg/kg in acute toxicity experiments. The LD50 of the intraperitoneal injection was 789 mg/kg, with a 95% confidence interval of 550-1000 mg/kg. The plasma attained its highest value (323.06 ng/mL) at 2 hours, according to Nrf2 activator-3 (5 mg/kg; intraperitoneal injection); Tmax, Cmax, AUC0-inf, F%, and T1/2 were 2 hours and 323.06 ng/mL, respectively; 2929.88 ng/mL*h, 28%, and 12.75 hours[1]. Tmax, Cmax, AUC0-inf, and T1/2 values for Nrf2 activator-3 (5 mg/kg;.iv) are 0.08 hours, 6911.14 ng/mL, 10182.73 ng/mL*h, and 8.26 hours, respectively [1]. In MCAO rats, Nrf2 activator-3 (3 mg/kg; 10 mg/kg; 30 mg/kg) decreases the extent of cerebral infarction, which lessens neurological impairments [1].
Cell Assay	Cell Viability Assay[1] Cell Types: PC12 cell Tested Concentrations: 1 μM, 5 μM, and 10 μM Incubation Duration: Experimental Results: Alleviated SNP-induced apoptosis in a concentration-dependent manner.
Animal Protocol	Animal/Disease Models: MCAO rats Doses: 3 mg/kg; 10 mg/kg; 30 mg/kg Route of Administration: intraperitoneal (ip)injection Experimental Results: Attenuated cerebral ischemic injury. (low dose: 16.37 ± 6.51%, medium dose: 14.49 ± 5.62%, high dose: 12.23 ± 8.50%), which was similar to the effect of Edaravone (12.77 ± 5.82%). Animal/Disease Models: MCAO rats Doses: 3 mg/kg; 10 mg/kg; 30 mg/kg Route of Administration: intraperitoneal (ip)injection Experimental Results: Attenuated cerebral ischemic injury. (low dose: 16.37 ± 6.51%, medium dose: 14.49 ± 5.62%, high dose: 12.23 ± 8.50%), which was similar to the effect of Edaravone (12.77 ± 5.82%).
References	[1]. Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential Nrf2 activators for the treatment of cerebral ischemic injury. Eur J Med Chem. 2022 Jun 5;236:114315.

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	2.3507 mL	11.7536 mL	23.5073 mL
	5 mM	0.4701 mL	2.3507 mL	4.7015 mL
	10 mM	0.2351 mL	1.1754 mL	2.3507 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.