Esaxerenone, formerly known as CS-3150, XL-550, is a nonsteroidal antimineralocorticoid which was discovered by Exelixis and is now under development by Daiichi Sankyo Company for the treatment of hypertension, essential hypertension, hyperaldosteronism, and diabetic nephropathies. It acts as a highly selective silent antagonist of the mineralocorticoid receptor (MR), the receptor for aldosterone, with greater than 1,000-fold selectivity for this receptor over other steroid hormone receptors, and 4-fold and 76-fold higher affinity for the MR relative to the existing antimineralocorticoids spironolactone and eplerenone.

Physicochemical Properties

Molecular Formula	C22H21F3N2O4S
Molecular Weight	466.4752
Exact Mass	466.117
CAS #	1632006-28-0
Related CAS #	1632006-28-0;880780-76-7;1072195-82-4 (+ isomer);1072195-83-5 (- isomer);
PubChem CID	25052023
Appearance	White to light yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	581.3±50.0 °C at 760 mmHg
Flash Point	305.4±30.1 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.581
LogP	3.15
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	32
Complexity	747
Defined Atom Stereocenter Count	0
InChi Key	NOSNHVJANRODGR-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H21F3N2O4S/c1-14-18(21(29)26-15-7-9-16(10-8-15)32(2,30)31)13-27(11-12-28)20(14)17-5-3-4-6-19(17)22(23,24)25/h3-10,13,28H,11-12H2,1-2H3,(H,26,29)
Chemical Name	1-(2-hydroxyethyl)-4-methyl-N-(4-(methylsulfonyl)phenyl)-5-(2-(trifluoromethyl)phenyl)-1H-pyrrole-3-carboxamide
Synonyms	Esaxerenone CS-3150 CS 3150 CS3150 XL-550 XL550 XL 550.
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 Vivo	The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increased with increasing dose after a single oral administration of 0.1, 0.3, 1, and 3 mg/kg esaxerenone. Esaxerenone's maximum plasma concentration (Tmax) can be reached in 2.0–4.5 hours. The systemic clearance (CL) and volume of distribution (Vss) at steady state following an intravenous injection of 0.1, 0.3, 1 and 3 mg/kg of esaxerenone were 3.53 to 6.69 mL/min/kg and 1.47 to 2.49 L/kg, respectively. Rats: 2.79 to 3.69 mL/min/kg; cynomolgus monkeys: 1.34 to 1.54 L/kg; and rats: 2.79 to 3.69 mL/min/kg. Rat urine and feces excreted 3.9% and 91.4%, respectively, of the dosed radioactive material within 168 hours of administration, for a total of 95.2%. In monkeys, 82.3% of the radioactive material expelled in feces and 11.5% in urine made up a total of 93.9% within 168 hours [1].
References	[1]. Pharmacokinetics, distribution, and disposition of esaxerenone, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist, in rats and monkeys. Xenobiotica. 2017 Dec;47(12):1090-1103.
Additional Infomation	Esaxerenone is under investigation in clinical trial NCT02722265 (Long-term Study of CS-3150 as Monotherapy or in Combination With Other Antihypertensive Drug in Japanese Patients With Essential Hypertension).

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~214.38 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 2.08 mg/mL (4.46 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1437 mL	10.7186 mL	21.4371 mL
	5 mM	0.4287 mL	2.1437 mL	4.2874 mL
	10 mM	0.2144 mL	1.0719 mL	2.1437 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.