VX-803 (M4344)

Catalog No.S9639 Synonyms: ATR inhibitor 2

For research use only.

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. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity.

VX-803 (M4344) Chemical Structure

CAS No. 1613191-99-3

Purity & Quality Control

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Biological Activity

Description 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. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity.
Targets
ATR [1]
(Cell-free assay)
Chk1 [1]
(Cell-free assay)
150 pM(Ki) 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. M4344 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.[1]

In vivo

In monotherapy efficacy studies M4344 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.[1]

Protocol (from reference)

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 541.55
Formula

C25H29F2N9O3

CAS No. 1613191-99-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CN(CCC1C(=O)N2CCN(CC2)C3COC3)C4=C(C=NC=C4NC(=O)C5=C6N=CC(=CN6N=C5N)F)F

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04149145 Not yet recruiting Drug: M4344+Niraparib Ovarian Cancer Recurrent University of Alabama at Birmingham December 2022 Phase 1
NCT04655183 Withdrawn Drug: Niraparib|Drug: M4344 Advanced Solid Tumor|Breast Cancer EMD Serono Research & Development Institute Inc.|Merck KGaA Darmstadt Germany|EMD Serono December 1 2020 Phase 1|Phase 2
NCT02278250 Completed Drug: M4344|Drug: Carboplatin Solid Tumor|Advanced Solid Tumor EMD Serono Research & Development Institute Inc.|Merck KGaA Darmstadt Germany|EMD Serono January 26 2015 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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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