NITD008 is a novel, potent and specific antiviral agent acting as a flaviviruse inhibitor and inhibits Dengue Virus Type 2 (DENV-2) with an EC50 of 0.64 μM. It has the potential for treatment of flavivirus infections.

Physicochemical Properties

Molecular Formula	C13H14N4O4
Molecular Weight	290.275
Exact Mass	290.101
CAS #	1044589-82-3
PubChem CID	44633776
Appearance	White to gray solid powder
Density	1.6±0.1 g/cm3
Boiling Point	631.8±55.0 °C at 760 mmHg
Flash Point	335.9±31.5 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.740
LogP	1.07
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	21
Complexity	455
Defined Atom Stereocenter Count	4
SMILES	C#C[C@]1([C@@H]([C@H](O[C@H]1N2C=CC3=C(N=CN=C32)N)CO)O)O
InChi Key	NKRAIOQPSBRMOV-NRMKKVEVSA-N
InChi Code	InChI=1S/C13H14N4O4/c1-2-13(20)9(19)8(5-18)21-12(13)17-4-3-7-10(14)15-6-16-11(7)17/h1,3-4,6,8-9,12,18-20H,5H2,(H2,14,15,16)/t8-,9-,12-,13-/m1/s1
Chemical Name	(2R,3R,4R,5R)-2-(4-Aminopyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-(hydroxymethyl)oxolane-3,4-diol
Synonyms	NITD 008NITD008 NITD-008
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	NITD008 exhibits efficacy against various different viruses, including as the Poisson virus, West Nile virus, dengue virus (DENV), and yellow fever virus. With an EC50 value of 0.64 μM, NITD008 suppresses DENV-2 in a dose-responsive manner; treatment with 9 μM of the chemical can reduce viral titers by more than 104 times [1]. With an EC50 value of 0.11 μM, NITD008 also suppresses the luciferase reporter replicon of the hepatitis C virus (HCV, genotype 1b), a member of the genus Hepatitis C virus [1].
ln Vivo	NITD008 has good pharmacokinetic qualities and is orally bioavailable. When prepared using 1.5 equimolar quantities of 6 N HCl, 1 N NaOH (pH adjusted to 3.5), and 100 mM citrate buffer (pH 3.5), NITD008 showed optimum pharmacokinetic characteristics. NITD008 has a long elimination half-life (t1/2=4.99 h) following intravenous administration due to its high volume of distribution (3.71 L/kg) and low systemic clearance (31.11 mL/min/kg). NITD008 is quickly absorbed (peak plasma concentration time = 0.5 h) upon po dose, with a maximum plasma concentration of 3 μM and a 48% bioavailability. NITD008 at a dose of 1 mg/kg did not lower mortality in mice immediately following viral infection; however, therapy at a dose of 3 mg/kg offered partial protection, and treatment at a dose of ≥10 mg/kg totally prevented the virus from killing the mice. NITD008 lowers cytokine increases, controls viremia peaks, and averts death [1].
References	[1]. An adenosine nucleoside inhibitor of dengue virus. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20435-9.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~172.25 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.61 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 (8.61 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 (8.61 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	3.4449 mL	17.2247 mL	34.4495 mL
	5 mM	0.6890 mL	3.4449 mL	6.8899 mL
	10 mM	0.3445 mL	1.7225 mL	3.4449 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.