Artefenomel (OZ439) is an orally bioactive, synthetic antimalarial compound containing the artemisinin pharmacophore and has a mechanism of action similar to artemisinin. Artefenomel has anti-viral effect against SARS-CoV-2.

Physicochemical Properties

Molecular Formula	C28H39NO5
Molecular Weight	469.612968683243
Exact Mass	469.283
CAS #	1029939-86-3
Related CAS #	1029939-86-3;1029939-87-4 (mesylate);1310917-29-3;
PubChem CID	24999143
Appearance	White to off-white solid powder
LogP	4.82
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	34
Complexity	680
Defined Atom Stereocenter Count	0
InChi Key	XLCNVWUKICLURR-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H39NO5/c1-3-26(31-14-11-29-9-12-30-13-10-29)4-2-22(1)23-5-7-27(8-6-23)32-28(34-33-27)24-16-20-15-21(18-24)19-25(28)17-20/h1-4,20-21,23-25H,5-19H2
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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	Proteins from Plasmodium falciparum are alkylated by artefenomel (OZ439) (10 μg/mL, 2 h) [1]. At dosages up to 300 μM, artefenomel (0.3-300 μM) decreases ACE2 expression in Vero cells in a dose-dependent manner without causing any cytotoxicity [2]. With an IC50 of 2.9 μM, artefenomel (33-100 μM) suppresses SARS-CoV-2 in a dose-dependent manner and entirely eliminates virus-induced CPE [2]. In pregnant Crl:CD(SD)BR rat embryos, artefenomel (0–10 µg/mL) damages red blood cells and causes anemia, which causes histological alterations (cell death) and macroscopic abnormalities [3].
Cell Assay	Cell Viability Assay[3] Cell Types: Embryos from pregnant Crl:CD(SD)BR rats Tested Concentrations: 0.1, 1, 2, 5, 7.5 and 10 µg/mL Incubation Duration: Experimental Results: demonstrated slightly shortened or slightly delayed tail Telencephalic vesicle loss occurs at 5 μg/mL, diminished circulating red blood cell numbers occur at 7.5 μg/mL, and cardiac arrhythmias occur at 10 μg/mL.
References	[1]. Monoclonal Antibodies That Recognize the Alkylation Signature of Antimalarial Ozonides OZ277 (Arterolane) and OZ439 (Artefenomel). ACS Infect Dis. 2016 Jan 8;2(1):54-61. [2]. Antimalarial Artefenomel Inhibits Human SARS-CoV-2 Replication in Cells while Suppressing the Receptor ACE2. [3]. Improved safety margin for embryotoxicity in rats for the new endoperoxide artefenomel (OZ439) as compared to artesunate. Birth Defects Res. 2018 Apr 17;110(7):553-578.
Additional Infomation	Artefenomel has been investigated for the treatment of Malaria.

Solubility Data

Solubility (In Vitro)

DMSO : ~4.2 mg/mL (~8.94 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	2.1294 mL	10.6471 mL	21.2943 mL
	5 mM	0.4259 mL	2.1294 mL	4.2589 mL
	10 mM	0.2129 mL	1.0647 mL	2.1294 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.