(R,S)-Ivosidenib ((R,S)-AG-120)

Cat No.:V74037 Purity: ≥98%

COA Product Data Instructions for use SDS

(R,S)-Ivosidenib ((R,S)-AG-120) is the less active enantiomer of Ivosidenib (AG-120).

(R,S)-Ivosidenib ((R,S)-AG-120) Chemical Structure CAS No.: 2070009-31-1
Product category: IDH

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

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Other Forms of (R,S)-Ivosidenib ((R,S)-AG-120):

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Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators

Product Description

(R,S)-Ivosidenib ((R,S)-AG-120) is the less active enantiomer of Ivosidenib (AG-120). Ivosidenib is a novel, small molecule, orally bioavailable inhibitor of mutated cytosolic isocitrate dehydrogenase 1 (IDH1) developed by Agios Pharmaceuticals and has been approved for the treatment of cancer in patients with IDH1 mutations. The mutated form of the IDH1 enzyme produces a metabolite, 2-hydroxyglutarate (2-HG), which is thought to play a role in the formation and progression of acute myeloid leukaemia (AML), gliomas and other cancers. Elevated 2-HG levels interfere with cellular metabolism and epigenetic regulation, thereby contributing to oncogenesis. Ivosidenib targets the IDH1 metabolic pathway to prevent a build-up of the oncometabolite 2-HG. On 7/20/2018, FDA approved Ivosidenib to treat patients with relapsed or refractory acute myeloid leukemia.

Biological Activity I Assay Protocols (From Reference)

Targets	IDH1R132H/isocitrate dehydrogenase 1 mutant
ln Vitro	Ivosidenib (AG-120) (0-13 μM; 48 hours) suppresses many IDH1-R132 mutants with comparable potency and IC50 values: IDH1-R132H (IC50=12 nM); IDH1-R132C (IC50=13 nM); IDH1-R132G (IC50=8 nM); IDH1-R132L (IC50=13 nM); and IDH1-R132S (IC50=12 nM), respectively [1].
ln Vivo	Twelve hours after therapy, AG-120 (gavage delivery; 50 mg/kg and 150 mg/kg) produced maximal inhibition (92.0% and 95.2% at the 50 mg/kg and 150 mg/kg dosages, respectively) and rapidly decreased tumor 2-HG concentrations [1].
References	[1]. Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1Mutant Cancers. ACS Med Chem Lett. 2018 Jan 19;9(4):300-305.

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

Physicochemical Properties

Molecular Formula	C28H22CLF3N6O3
Molecular Weight	582.96
Exact Mass	582.139
Elemental Analysis	C, 57.69; H, 3.80; Cl, 6.08; F, 9.78; N, 14.42; O, 8.23
CAS #	2070009-31-1
Related CAS #	Ivosidenib;1448347-49-6;IDH1 Inhibitor 8;1448346-63-1
PubChem CID	121230976
Appearance	White to off-white solid
Density	1.5±0.1 g/cm3
Boiling Point	854.3±65.0 °C at 760 mmHg
Flash Point	470.4±34.3 °C
Vapour Pressure	0.0±3.2 mmHg at 25°C
Index of Refraction	1.651
LogP	0.38
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	41
Complexity	1050
Defined Atom Stereocenter Count	2
SMILES	N1(C2=NC=CC(C#N)=C2)C(=O)CC[C@H]1C(N([C@H](C1=CC=CC=C1Cl)C(NC1CC(F)(F)C1)=O)C1=CC(F)=CN=C1)=O
InChi Key	WIJZXSAJMHAVGX-WIOPSUGQSA-N
InChi Code	InChI=1S/C28H22ClF3N6O3/c29-21-4-2-1-3-20(21)25(26(40)36-18-11-28(31,32)12-18)37(19-10-17(30)14-34-15-19)27(41)22-5-6-24(39)38(22)23-9-16(13-33)7-8-35-23/h1-4,7-10,14-15,18,22,25H,5-6,11-12H2,(H,36,40)/t22-,25+/m0/s1
Chemical Name	(S)-N-((R)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide
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: 3.33 mg/mL (5.71 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 0.33 mg/mL (0.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 3.3 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. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: 3.33 mg/mL (5.71 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.33 mg/mL (0.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 3.3 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.

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7154 mL	8.5769 mL	17.1538 mL
	5 mM	0.3431 mL	1.7154 mL	3.4308 mL
	10 mM	0.1715 mL	0.8577 mL	1.7154 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

Mass

Concentration

Volume

Molecular Weight*

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

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

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.

Concentration (Start)

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Concentration (End)

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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

Total molecular weight

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.

Volume (to add to vial)

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Desired Reconstitution Concentration

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
Click the “Calculate” button
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)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

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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.)

% DMSO

% Tween 80

% ddH₂O

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.