ALS–8112

Cat No.:V10873 Purity: ≥98%

COA Product Data Instructions for use SDS

ALS-8112 is a potent and specific respiratory syncytial virus (RSV) polymerase inhibitor.

ALS–8112 Chemical Structure CAS No.: 1445379-92-9
Product category: New1

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of ALS–8112:

Lumicitabine

Official Supplier of:

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Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators

Product Description

ALS-8112 is a potent and specific respiratory syncytial virus (RSV) polymerase inhibitor. The 5'-triphosphate form of ALS-8112 inhibits RSV polymerase with IC50 of 0.02 μM.

Biological Activity I Assay Protocols (From Reference)

ln Vitro	The drug's active form, ALS-8112 -TP, disables RSV polymerase by causing RNA synthesis to terminate at the 5'-triphosphate [2]. After entering different kinds of respiratory tract epithelial cells, ALS-008112 is phosphorylated to produce intracellular nucleoside triphosphates, which have a half-life of roughly 29. RSV replication is similarly inhibited by hourly nucleoside triphosphates via chain termination [3]. With an IC50 of 0.020 ± 0.008 μM, ALS-8112 is an external RSV replicating ubiquitin ALS-8112-TP that proportionally suppresses the RSV–RNP complex's RNA regulatory action [4].
References	[1]. Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection. J Med Chem. 2015 Feb 26;58(4):1862-78. [2]. Activation Pathway of a Nucleoside Analog Inhibiting Respiratory Syncytial Virus Polymerase. ACS Chem Biol. 2017 Jan 20;12(1):83-91. [3]. Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2015 Nov 19;373(21):2048-58. [4]. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate. PLoS Pathog. 2015 Jun 22;11(6):e1004995.

ln Vitro

The drug's active form, ALS-8112 -TP, disables RSV polymerase by causing RNA synthesis to terminate at the 5'-triphosphate [2]. After entering different kinds of respiratory tract epithelial cells, ALS-008112 is phosphorylated to produce intracellular nucleoside triphosphates, which have a half-life of roughly 29. RSV replication is similarly inhibited by hourly nucleoside triphosphates via chain termination [3]. With an IC50 of 0.020 ± 0.008 μM, ALS-8112 is an external RSV replicating ubiquitin ALS-8112-TP that proportionally suppresses the RSV–RNP complex's RNA regulatory action [4].

References

[1]. Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection. J Med Chem. 2015 Feb 26;58(4):1862-78.

[2]. Activation Pathway of a Nucleoside Analog Inhibiting Respiratory Syncytial Virus Polymerase. ACS Chem Biol. 2017 Jan 20;12(1):83-91.

[3]. Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2015 Nov 19;373(21):2048-58.

[4]. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate. PLoS Pathog. 2015 Jun 22;11(6):e1004995.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C10H13CLFN3O4
Molecular Weight	293.6793
Exact Mass	293.057
CAS #	1445379-92-9
Related CAS #	Lumicitabine;1445385-02-3
PubChem CID	71621663
Appearance	White to off-white solid powder
Density	1.8±0.1 g/cm3
Boiling Point	532.8±60.0 °C at 760 mmHg
Flash Point	276.0±32.9 °C
Vapour Pressure	0.0±3.2 mmHg at 25°C
Index of Refraction	1.668
LogP	-0.42
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	19
Complexity	447
Defined Atom Stereocenter Count	4
SMILES	C1=CN(C(=O)N=C1N)[C@H]2[C@@H]([C@@H]([C@](O2)(CO)CCl)O)F
InChi Key	AWSRKKBIPSQHOJ-IBCQBUCCSA-N
InChi Code	InChI=1S/C10H13ClFN3O4/c11-3-10(4-16)7(17)6(12)8(19-10)15-2-1-5(13)14-9(15)18/h1-2,6-8,16-17H,3-4H2,(H2,13,14,18)/t6-,7+,8-,10-/m1/s1
Chemical Name	4-amino-1-[(2R,3R,4R,5R)-5-(chloromethyl)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
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)

Solubility Data

Solubility (In Vitro)	DMSO : ≥ 47 mg/mL (~160.04 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.5 mg/mL (8.51 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 (8.51 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO : ≥ 47 mg/mL (~160.04 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.51 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (8.51 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.4051 mL	17.0253 mL	34.0507 mL
	5 mM	0.6810 mL	3.4051 mL	6.8101 mL
	10 mM	0.3405 mL	1.7025 mL	3.4051 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.

Calculator

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.