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VX-803 (M4344) ATM/ATR inhibitor

Name: VX-803 (M4344)
Brand: Selleck Chemicals
SKU: S9639
Availability: InStock
Rating: 5 (9 reviews)

Cat.No.S9639

VX-803 (M4344, ATR inhibitor 2) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. This compound potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. It exhibits potential antineoplastic activity.

Chemical Structure

Molecular Weight: 541.55

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Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	PI3K Akt mTOR GSK-3 DNA-PK AMPK PDPK1 PTEN PP2A PDK
Other ATM/ATR Inhibitors	Ceralasertib (AZD6738) AZD1390 Berzosertib (VE-822) Lartesertib (M4076) Camonsertib (RP-3500) KU-60019 KU-55933 VE-821 AZ20 AZD0156

Solubility

In vitro
Batch:

DMSO : 15 mg/mL (27.69 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.300mg/ml (0.55mM)	Taking the 1 mL working solution as an example, add 50 μL of 6 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.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.300mg/ml (0.55mM)	Taking the 1 mL working solution as an example, add 50 μL of 6 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.

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.

Chemical Information, Storage & Stability

Molecular Weight	541.55	Formula	C₂₅H₂₉F₂N₉O₃	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1613191-99-3	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	ATR inhibitor 2			Smiles	C1CN(CCC1C(=O)N2CCN(CC2)C3COC3)C4=C(C=NC=C4NC(=O)C5=C6N=CC(=CN6N=C5N)F)F

Mechanism of Action

Targets/IC₅₀/Ki	ATR (Cell-free assay) 150 pM(Ki) Chk1 (Cell-free assay) 8 nM
In vitro	M4344 is determined to be an adenosine triphosphate (ATP)-competitive, highly potent, and tight-binding inhibitor of ATR with a Ki of < 150 pM. Minimal inhibitory activity is observed against a large panel of unrelated protein kinases, with 308 of 312 kinases tested having a measured Ki corresponding to more than 100-fold selectivity. This compound potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with an IC50 of 8 nM. Profiling on a selected set of cancer cell lines shows synergy with several types of DNA damaging chemotherapeutics as well as PARP1/2 and CHK1 inhibitors.
In vivo	In monotherapy efficacy studies this compound shows tumor stasis to regression in tumor models with alternative lengthening of telomeres (ALT). In combination with PARP inhibitors, tumor regression can be observed in triple-negative breast cancer xenograft models.
References	[1] https://cancerres.aacrjournals.org/content/79/13_Supplement/369 [2] https://aacrjournals.org/cancerres/article/79/13_Supplement/369/635928/Abstract-369-Antitumor-activity-of-M4344-a-potent [3] https://pubmed.ncbi.nlm.nih.gov/36413415/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04149145	Withdrawn	Ovarian Cancer Recurrent	University of Alabama at Birmingham	May 2023	Phase 1
NCT04655183	Withdrawn	Advanced Solid Tumor\|Breast Cancer	EMD Serono Research & Development Institute Inc.\|Merck KGaA Darmstadt Germany\|EMD Serono	December 1 2020	Phase 1\|Phase 2

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