AER-271 is a novel and potent aquaporin-4 (AQP4) inhibitor that blocks acute cerebral edema and improves early outcome in a pediatric model of asphyxial cardiac arrest. Treatment with AER-271 ameliorated early cerebral edema measured at 3 h after CA vs vehicle treated rats. This treatment also attenuated early NDS. In contrast to rats treated with vehicle after CA, rats treated with AER-271 did not develop significant neuronal death or neuroinflammation as compared to sham.

Physicochemical Properties

Molecular Formula	C15H9CLF6NO5P
Molecular Weight	463.6528
Exact Mass	462.981
Elemental Analysis	C, 38.86 H, 1.96 Cl, 7.65 F, 24.59 N, 3.02 O, 17.25 P, 6.68
CAS #	634913-39-6
PubChem CID	10412080
Appearance	White to off-white solid powder
LogP	3.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	29
Complexity	620
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C([H])C(=C(C=1[H])C(N([H])C1C([H])=C(C(F)(F)F)C([H])=C(C(F)(F)F)C=1[H])=O)OP(=O)(O[H])O[H]
InChi Key	WSHXPHFIHYXZKC-UHFFFAOYSA-N
InChi Code	InChI=1S/C15H9ClF6NO5P/c16-9-1-2-12(28-29(25,26)27)11(6-9)13(24)23-10-4-7(14(17,18)19)3-8(5-10)15(20,21)22/h1-6H,(H,23,24)(H2,25,26,27)
Chemical Name	2-{[3,5-Bis(trifluoromethyl) phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate
Synonyms	AER 271 AER-271 AER271
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	In vivo, endogenous phosphatases change AER-271 into AER-270. In a juvenile model of wild-type respiratory cardiac arrest, AER-271 causes cerebral edema and enhances early outcomes [1]. In an emergency animal model of cerebral stroke, AER-271 improves neurological outcomes and decreases cerebral edema. In a localized stroke model, administration of AER-271 (5 mg/kg; i.p.) resulted in better outcomes and decreased cerebral edema [2].
Animal Protocol	Animal/Disease Models: Male mice (C57BL/6J, 8-12 weeks old, 25- 30 g) [2] Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection Treatment Experimental Results: Good effect, mean neurological score of 0.89 Compared with control mice receiving vehicle, mean neurological score of ±0.31 2.50±0.62.
References	[1]. The aquaporin-4 inhibitor AER-271 blocks acute cerebral edema and improves early outcome in a pediatric model of asphyxial cardiac arrest. Pediatr Res. 2019 Mar;85(4):511-517. [2]. Functionalized Phenylbenzamides Inhibit Aquaporin-4 Reducing Cerebral Edema and Improving Outcome in Two Models of CNS Injury. Neuroscience. 2019 Apr 15;404:484-498.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~269.60 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.49 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 (4.49 mM) (saturation unknown) 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	2.1568 mL	10.7840 mL	21.5680 mL
	5 mM	0.4314 mL	2.1568 mL	4.3136 mL
	10 mM	0.2157 mL	1.0784 mL	2.1568 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.