RV521 is an orally bioactive, highly potent small-molecule inhibitor of RSV (respiratory syncytial virus) fusion protein. It is with promising pharmaceutical properties and is currently in clinical development for the treatment of RSV disease in paedriatrics, the elderly and immune-compromised patients. RV521 targets (RSV) fusion which is a surface protein that mediates RSV binding to cellular receptors. RSV infection has been an unmet medical need and RV521 is being developed to treat RSV in patients suffering with severe disease, including neonates, the elderly, the immunocompromised and those with underlying cardiovascular or respiratory disease.

Physicochemical Properties

Molecular Formula	C23H22F4N4O
Molecular Weight	446.440598964691
Exact Mass	446.172
CAS #	1903763-82-5
Related CAS #	Sisunatovir hydrochloride;1903763-83-6
PubChem CID	132016492
Appearance	White to off-white solid powder
LogP	3.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	32
Complexity	715
Defined Atom Stereocenter Count	0
SMILES	FC1C=CC2=C(C=1)N(CC1=NC3C=C(CN)C=CC=3N1CCCC(F)(F)F)C(C12CC1)=O
InChi Key	JOPCJJSYRPUEDS-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H22F4N4O/c24-15-3-4-16-19(11-15)31(21(32)22(16)7-8-22)13-20-29-17-10-14(12-28)2-5-18(17)30(20)9-1-6-23(25,26)27/h2-5,10-11H,1,6-9,12-13,28H2
Chemical Name	1''-((5-(aminomethyl)-1-(4,4,4-trifluorobutyl)-1H-benzo[d]imidazol-2-yl)methyl)-6''-fluorospiro[cyclopropane-1,3''-indolin]-2''-one
Synonyms	RV521; RV-521; RV 521
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	In vitro activity: Kinase Assay: Cell Assay:
ln Vivo
Animal Protocol
References	[1]. A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein. Antimicrob Agents Chemother. 2020;64(2):e01884-19. Published 2020 Jan 27.
Additional Infomation	Sisunatovir is under investigation in clinical trial NCT04267822 (Study of RV521 in the Treatment of Adult Subjects Who Have Undergone HCT With an URTI With RSV). Sisunatovir is an orally available, small molecule inhibitor of human respiratory syncytial virus (RSV) fusion protein (F protein), with potential antiviral activity. Upon oral administration, sisunatovir specifically targets and binds to RSV-F protein on the viral surface, which inhibits RSV-F protein-mediated fusion with the host cell membrane and prevents viral entry. This blocks RSV replication, reduces viral load, and decreases the severity of the disease. RSV-F protein, a viral surface glycoprotein, plays a key role in RSV fusion with and entry into target cells.

Solubility Data

Solubility (In Vitro)

DMSO: 10 mM Water:< 1mg/mL Ethanol:< 1mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.60 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 25.0 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: ≥ 2.5 mg/mL (5.60 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.60 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 25.0 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	2.2399 mL	11.1997 mL	22.3994 mL
	5 mM	0.4480 mL	2.2399 mL	4.4799 mL
	10 mM	0.2240 mL	1.1200 mL	2.2399 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.