Dexfadrostat ((R)-Fadrozole) is a potent nonsteroidal inhibitor. Dexfadrostat also inhibits human placental aromatase (pIC50 = 6.17) and aldosterone biosynthesis. Dexfadrostat reverses cardiac fibrosis in rats with spontaneous hypertensive heart failure.

Physicochemical Properties

Molecular Formula	C14H13N3
Molecular Weight	223.27312
Exact Mass	223.11
Elemental Analysis	C, 75.31; H, 5.87; N, 18.82
CAS #	102676-87-9
Related CAS #	Fadrozole hydrochloride;102676-31-3;Fadrozole;102676-47-1;Fadrozole hydrochloride hemihydrate;176702-70-8; 102676-87-9 (Dexfadrostat free base); 131863-75-7 (Dexfadrostat HCl)
PubChem CID	9815923
Appearance	Typically exists as Light yellow to yellow solid at room temperature
Density	1.2±0.1 g/cm3
Boiling Point	481.7±38.0 °C at 760 mmHg
Flash Point	245.1±26.8 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.662
LogP	1.9
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	1
Heavy Atom Count	17
Complexity	311
Defined Atom Stereocenter Count	1
SMILES	C1C[C@@H](N2C=NC=C2C1)C3=CC=C(C=C3)C#N
InChi Key	CLPFFLWZZBQMAO-CQSZACIVSA-N
InChi Code	InChI=1S/C14H13N3/c15-8-11-4-6-12(7-5-11)14-3-1-2-13-9-16-10-17(13)14/h4-7,9-10,14H,1-3H2/t14-/m1/s1
Chemical Name	4-[(5R)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl]benzonitrile
Synonyms	Dexfadrostat; (R)-Fadrozole; Fadrozole, (R)-; R-FADROZOLE; 102676-87-9; (+)-Fadrozole; Dexfadrostat [INN]; IC1B8751F6;
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	pIC50: 6.17 (human placental aromatase)
ln Vitro	The strong aromatase inhibitory action of dexfadrostat was attributed to the (-)-enantiomer with the S-absolute configuration[1].
ln Vivo	Dexfadrostat ((R)-fadrozole; 0.24 and 1.2 mg/kg; daily; oral) and (S)-fadrozole both lower plasma levels of aldosterone, but only S-fadrozole decreased the rate of aldosterone excretion in the urine[2]. S-fadrozole lacked an antifibrotic effect, but dexfadrostat (0.24 and 1.2 mg/kg; daily; oral) successfully reverses preexisting left ventricular interstitial fibrosis by 50% (compared to 42% for canrenoate)[2].
Enzyme Assay	The enantiomers of the potent nonsteroidal inhibitor of aromatase fadrozole hydrochloride 3 have been separated and their absolute configuration determined by X-ray crystallography. On the basis of a molecular modeling comparison of the active enantiomer 4 and one of the most potent steroidal inhibitors reported to date, (19R)-10-thiiranylestr-4-ene-3,17-dione, 7, a model describing the relative binding modes of the azole-type and steroidal inhibitors of aromatase at the active site of the enzyme is proposed. It is suggested that the cyanophenyl moiety present in the most active azole inhibitors partially mimics the steroid backbone of the natural substrate for aromatase, androst-4-ene-3,17-dione, 1. The synthesis and biological testing of novel analogues of 3 used to define the accessible and nonaccessible volumes to ligands in the model of the active site of aromatase are reported.[1]
Animal Protocol	Animal/Disease Models: SHHF rats[2] Doses: 0.24 and 1.2 mg/kg Route of Administration: Daily; oral Experimental Results: diminished plasma aldosterone levels and reversed preexistent left ventricular interstitial fibrosis.
References	[1]. Aromatase inhibitors: synthesis, biological activity, and binding mode of azole-type compounds. J Med Chem. 1993;36(10):1393-1400. [2]. Fadrozole reverses cardiac fibrosis in spontaneously hypertensive heart failure rats: discordant enantioselectivity versus reduction of plasma aldosterone. Endocrinology. 2008;149(1):28-31.
Additional Infomation	A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.

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	4.4789 mL	22.3944 mL	44.7888 mL
	5 mM	0.8958 mL	4.4789 mL	8.9578 mL
	10 mM	0.4479 mL	2.2394 mL	4.4789 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.