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Vorasidenib (AG-881)

Catalog No.S8611 Purity:99.99%

Vorasidenib (AG-881) is an orally available inhibitor of mutated forms of both isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2).

Vorasidenib (AG-881) Chemical Structure

CAS No. 1644545-52-7

Purity & Quality Control

Batch: Purity: 99.99%

99.99

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Signaling Pathway

Dehydrogenase Signaling Pathway

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
U87MG	Antiproliferative assay	72 hrs	Antiproliferative activity against human U87MG cells expressing pLVX-IDH2 R140Q mutant after 72 hrs by celltiterglo reagent based assay, IC50<0.05μM	29847930
TS603	Antiproliferative assay	72 hrs	Antiproliferative activity against human TS603 cells harboring IDH2 R140Q mutant after 72 hrs by celltiterglo reagent based assay, IC50<0.05μM	29847930
HT1080	Antiproliferative assay	72 hrs	Antiproliferative activity against human HT1080 cells after 72 hrs by celltiterglo reagent based assay, IC50<0.05μM	29847930
Sf9	Function assay	1 hr	Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132H mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presenc, IC50<0.05μM	ChEMBL
Sf9	Function assay	1 hr	Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132C mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presenc, IC50<0.05μM	ChEMBL
Sf9	Function assay	1 hr	Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry, IC50<0.05μM	ChEMBL
Sf9	Function assay	1 hr	Inhibition of DH1 R132C mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry, IC50<0.05μM	ChEMBL
Sf9	Function assay	1 hr	Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofa, IC50<0.05μM	ChEMBL
HT1080	Function assay	48 hrs	Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method, IC50<0.05μM	ChEMBL
U87MG	Function assay	48 hrs	Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method, IC50<0.05μM	ChEMBL
TS603	Function assay	48 hrs	Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method, IC50<0.05μM	ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description

Vorasidenib (AG-881) is an orally available inhibitor of mutated forms of both isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2).

Targets

IDH1 ^[1]

IDH2 ^[1]

In vitro
In vitro	Pan-IDH1/2 inhibitor (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo models^[1]. Upon administration, pan-IDH mutant inhibitor AG-881 specifically inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations^[2].

In Vivo
In vivo	AG-881 fully penetrates the blood-brain barrier. AG-881 has been developed and is in early phase I testing for patients with IDH mutation-positive hematologic malignancies and solid tumors, including glioma^[3].

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05609994	Not yet recruiting	Low Grade Glioma of Brain	Katy Peters MD PhD\|Servier\|Duke University	June 2024	Phase 1
NCT05674474	Completed	Hepatic Impairment	Institut de Recherches Internationales Servier\|Servier	March 14 2023	Phase 1
NCT05484622	Recruiting	Astrocytoma	Institut de Recherches Internationales Servier\|Merck Sharp & Dohme LLC\|Servier	January 20 2023	Phase 1
NCT04145128	Completed	Healthy Volunteers	Agios Pharmaceuticals Inc.	October 2 2019	Phase 1

References
[1] Fujii, et al. Discov Med. 2016, 21(117):373-80. [2] Upadhyay VA, et al. Pharmacol Ther. 2017, 177:123-128. [3] Dang L, et al. Ann Oncol. 2016, 27(4):599-608.

References

Chemical Information & Solubility

Molecular Weight	414.74	Formula	C₁₄H₁₃ClF₆N₆
CAS No.	1644545-52-7	SDF	Download Vorasidenib (AG-881) SDF
Smiles	CC(C(F)(F)F)NC1=NC(=NC(=N1)C2=NC(=CC=C2)Cl)NC(C)C(F)(F)F
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 82 mg/mL ( (197.71 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 82 mg/mL

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.					In vivo Formulation Calculator
	Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	1.36mg/ml (3.28mM)	Taking the 1 mL working solution as an example, add 50 μL of 27.2 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.	In vivo Formulation Calculator
Clear solution	5% DMSO 1 95% Corn oil	0.41mg/ml (0.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 8.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	1.0mg/ml (2.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.05mg/ml (4.94mM)	Taking the 1 mL working solution as an example, add 50 μL of 41 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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