α-Dihydroartemisinin is a natural product that can be found in artemisinin. α-Dihydroartemisinin also shows antimalarial activity.

Physicochemical Properties

Molecular Formula	C15H24O5
Molecular Weight	284.35
Exact Mass	284.162
CAS #	81496-81-3
PubChem CID	11358077
Appearance	Typically exists as solid at room temperature
Density	1.3±0.1 g/cm3
Boiling Point	375.6±42.0 °C at 760 mmHg
Melting Point	164-165
Flash Point	181.0±27.9 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.543
LogP	2.6
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	0
Heavy Atom Count	20
Complexity	415
Defined Atom Stereocenter Count	8
SMILES	C[C@@H]1CC[C@H]2[C@H]([C@@H](O[C@H]3[C@@]24[C@H]1CC[C@](O3)(OO4)C)O)C
InChi Key	BJDCWCLMFKKGEE-KDTBHNEXSA-N
InChi Code	InChI=1S/C15H24O5/c1-8-4-5-11-9(2)12(16)17-13-15(11)10(8)6-7-14(3,18-13)19-20-15/h8-13,16H,4-7H2,1-3H3/t8-,9-,10+,11+,12-,13-,14-,15-/m1/s1
Chemical Name	(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
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

ADME/Pharmacokinetics	Absorption, Distribution and Excretion The reported oral bioavailability of Artenimol was reported to be 45% in healthy adults. The observed Tmax was 1-2 h This is known to increase in malaria infected patients which could be attributed to reduced metabolism by the liver or the drug's collection in infected erythrocytes. Artenimol was obeserved to have flip-flop kinetics with an overall absorption half-life of 1.04 h. When administered with food the AUC for Artenimol increases by 144%. Cmax was observed to increase by 129% but was not found to be statistically significant. Food was observed to delay Tmax by 1 h. Artenimol is eliminated via metabolism to glucuronide conjugates. There is little data on elimination of Artenimol but elimination of unchanged artemisinin compounds in feces and urine has been reported to be negligible. Artenimol was observed to have a mean apparent volume of distribution of 0.801 L/kg in adult patients and 0.705 L/kg in pediatric patients wit *P. falciparum malaria. Artenimol was observed to have a mean apparent clearance of 1.340 L/h/kg in adult patients and 1.450 L/h/kg in pediatric patients with *P. falciparum malaria. Metabolism / Metabolites The primary metabolite of Artenimol is the glucuronide conjugate, α-artenimol-β-glucuronide. It is largely metabolized by UGT1A9 with some contribution by UGT2B7. Biological Half-Life Artenimol was reported to have a half life of elimination of approximately 1 h.
Toxicity/Toxicokinetics	Protein Binding Artenimol has been reported to be 44-93% bound to plasma proteins. The identity of these proteins has not been reported.
References	[1].Synthesis of dihydroartemisinin using Ni/TiO2 catalyst prepared by sol gel method. Journal of Applied Pharmaceutical Science, 2014, 4(1), Article 40101.
Additional Infomation	Dihydroartemisinin (DHA) is an artemisinin derivative. Artenimol is an artemisinin derivative and antimalarial agent used in the treatment of uncomplicated *Plasmodium falciparum* infections. It was first authorized for market by the European Medicines Agency in October 2011 in combination with [DB13941] as the product Eurartesim. Artemisinin combination therapy is highly effective against malaria and stongly recommended by the World Health Organization. .alpha.-dihydroartemisinin is an Antimalarial. Artenimol is an active metabolite of artesunate, with anti-malarial activity, and potential insulin sensitivity-improving, anti-inflammatory, immunomodulating and antineoplastic activities. Upon administration of artenimol and the hydrolysis of its active endoperoxide bridge moiety by liberated heme in parasite-infected red blood cells (RBCs), reactive oxygen species (ROS) and carbon-centered radicals form, which damage and kill parasitic organisms. Artenimol may also increase insulin sensitivity and improve insulin resistance. In addition, artenimol induces the 26S proteasome-mediated degradation of the androgen receptor (AR), thereby lowering AR expression, which may prevent androgen-responsive cellular proliferation. It also reduces luteinizing hormone LH) and testosterone levels, and may improve polycystic ovary syndrome (PCOS). In addition, artenimol may modulate the immune system and may inhibit tumor cell proliferation through various apoptotic and non-apoptotic pathways. See also: Artenimol (annotation moved to). Drug Indication For the treatment of uncomplicated *Plasmodium falciparum* infection in adults, children, and infants aged 6 months and up weighing over 5 kg. Used in combination with [DB13941]. FDA Label Mechanism of Action Artemisinins, including Artenimol which is a major active metabolite of many artemisinins, are thought to act via a common mechanism. While the exact mechanism of action is not certain, theories exist as to how artemisinins produce their antimalarial effect. Artemisinins are believed to bind to haem within the *P. falciparum* parasite. The source of this haem varies with the life stage of the parasite. When the parasite is in the early ring stage artemisinins are believed to bind haem produced by the parasite's haem biosynthesis pathway. In later stages artemisinins likely bind to haem released by haemoglobin digestion. Once bound to haem, artemisinins are thought to undergo activation involving ferrous iron via reductive scission which splits the endoperoxide bridge to produce a reactive oxygen. This reactive oxygen is thought to undergo a subsequent intramolecular hydrogen abstraction to produce a reactive carbon radical. The carbon radical is believed to be the source of the drugs potent activity against *P. falciparum* by alkylating a wide array of protein targets. The nature and magnitude of the effect on specific protein function as a result of this alkylation is unknown. One target which has been the focus of research is the sarco/endoplasmic reticulum Ca2+ ATPase pump of *P. falciparum*. Artemisinins have been found to irreversably bind to and inhibit this protein at a binding site similar to that of Thapsigargin. The mechanism is likely the same as for other proteins, namely alkylation via the carbon radical intermediate. Artemisinins appear to preferentially collect in infected erythrocytes, concentrating the drug by several hundred-fold compared to uninfected cells. This may play a role in why little alkylation is seen in uninfected erythrocytes. Pharmacodynamics Artenimol is thought to form a reactive carbon radical intermediate which kills *P. falciparum* through alkylation of a wide array of proteins.

Solubility Data

Solubility (In Vitro)

Typically soluble in DMSO (e.g. 10 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	3.5168 mL	17.5840 mL	35.1679 mL
	5 mM	0.7034 mL	3.5168 mL	7.0336 mL
	10 mM	0.3517 mL	1.7584 mL	3.5168 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.