Obeldesivir (GS-5245; ATV-006; SHEN26) is an orally bioactive antiviral agent and ester prodrug of GS-441524 under investigation for COVID-19. It inhibits the replication of SARS-CoV-2 and may be used for SARS-CoV-2 treatment.

Physicochemical Properties

Molecular Formula	C16H19N5O5
Molecular Weight	361.35
Exact Mass	361.138
CAS #	2647441-36-7
PubChem CID	162513664
Appearance	White to off-white solid powder
LogP	-0.3
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	595
Defined Atom Stereocenter Count	4
SMILES	C([C@]1(C2=CC=C3C(=NC=NN23)N)[C@@H]([C@H](O)[C@@H](COC(=O)C(C)C)O1)O)#N
InChi Key	YIHPGVCWGSURHO-VSBTWAGUSA-N
InChi Code	InChI=1S/C16H19N5O5/c1-8(2)15(24)25-5-10-12(22)13(23)16(6-17,26-10)11-4-3-9-14(18)19-7-20-21(9)11/h3-4,7-8,10,12-13,22-23H,5H2,1-2H3,(H2,18,19,20)/t10-,12-,13-,16+/m1/s1
Chemical Name	[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methyl 2-methylpropanoate
Synonyms	Obeldesivir GS-5245 ATV-006 SHEN-26GS5245 ATV006 SHEN26
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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	Obeldesivir (0.001-100 μM; 48 h; Vero E6 cells) prevents both the pathogenic and real SARS-CoV-2 variants from replicating. Obeldesivir's effectiveness in blocking the replication of Delta and Omicron variants is improved overall by >4 and >12 times, respectively, with EC50 values of 0.349 μM and 0.106 μM[1].
ln Vivo	The pharmacokinetic profiles of beldesivir (5–25 mg/kg; po and iv) in Sprague Dawley rats are favorable, with a high oral bioavailability (F%) of 81.5% and a maximum blood concentration (Cmax) of 8.2 μM[1]. Obeldesivir (250–500 mg/kg; po; daily, 4 days; Ad5-hACE2 and hACE2 knock-in mice) has antiviral activity and prevents the replication of SARS-CoV-2 in mouse models[1]. K18-hACE2 mice are protected and lung damage is decreased by kg; po; daily, for 10 days[1]. In K18-hACE2 mice, obeldesivir (10–150 mg/kg; po; daily, for 3 days) decreases virus titers and lung damage brought on by Delta variant infection[1].
Animal Protocol	Animal/Disease Models: Sprague Dawley rats[1] Doses: 5 and 25 mg/kg Route of Administration: Oral administration (25 mg/kg) and intravenous (iv) injection (5 mg/kg) Experimental Results: 1.19 parameters iv (5 mg/kg) po (25 mg/kg) AUClast (μM·h) 5.6 22.8 T1/2 (h) 1.5 1.2 Tmax (h) 0.5 Cmax (μM) 8.7 8.2 F % 81.5 Animal/Disease Models: hACE2 knock- in and Ad5-hACE2 mice[1] Doses: 250 and 500 mg/kg Route of Administration: Oral administration; daily, for 4 days Experimental Results: Inhibited gRNA and sgRNA, which is Biomarkers of coronavirus replication. decreased the viral load and pathological damage of the lung. Animal/Disease Models: K18-hACE2 mice[1] Doses: 100 and 250 mg/kg Route of Administration: Oral administration; daily, for 10 days Experimental Results: decreased viral RNA and increased the survival rate of mice. decreased evidence of lung pathology and the production of inflammatory cytokines and chemokines in the lung tissues. Animal/Disease Models: K18-hACE2 mice[1] Doses: 10, 30, 80 and 150 mg/kg Route of Administration: Oral administration; daily, for 3 days Experimental Results: decreased viral load in a d
References	[1]. The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants. Sci Transl Med. 2022 May 17:eabm7621.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~691.85 mM)

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	2.7674 mL	13.8370 mL	27.6740 mL
	5 mM	0.5535 mL	2.7674 mL	5.5348 mL
	10 mM	0.2767 mL	1.3837 mL	2.7674 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.