VX-803 (M4344) - Moligand™, 10mM in DMSO , Serine-protein kinase ATR inhibitor, CAS No.1613191-99-3, Serine-protein kinase ATR inhibitor

CAS: 1613191-99-3 Cat. No.: V421944 Molecular Weight: 541.55 PubChem CID: 86720912

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

2-amino-6-fluoro-N-[5-fluoro-4-[4-[4-(oxetan-3-yl)piperazine-1-carbonyl]piperidin-1-yl]pyridin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide Computed by Lexi | 2-amino-6-fluoro-N-[5-fluoro-4-[4-[4-(oxetan-3-yl)piperazine-1-carbonyl]-1-piperidyl]-3-pyridyl]

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

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

Targets

ATR (Cell-free assay); Chk1 (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.

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.

Specifications

Synonyms

2-amino-6-fluoro-N-[5-fluoro-4-[4-[4-(oxetan-3-yl)piperazine-1-carbonyl]piperidin-1-yl]pyridin-3-yl]pyrazolo[1, 5-a]pyrimidine-3-carboxamide Computed by Lexi | 2-amino-6-fluoro-N-[5-fluoro-4-[4-[4-(oxetan-3-yl)piperazine-1-carbonyl]-1-piperidyl]-3-pyridyl]

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

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-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Serine-protein kinase ATR inhibitor

Product Properties

• ALogP: -0.338
• HBD Count: 2
• Rotatable Bond: 5

Names and Identifiers

• Pubchem Sid: 528767675
• Canonical Smiles: C1CN(CCC1C(=O)N2CCN(CC2)C3COC3)C4=C(C=NC=C4NC(=O)C5=C6N=CC(=CN6N=C5N)F)F
• IUPAC Name: 2-amino-6-fluoro-N-[5-fluoro-4-[4-[4-(oxetan-3-yl)piperazine-1-carbonyl]piperidin-1-yl]pyridin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
• InChIKey: QAYHKBLKSXWOEO-UHFFFAOYSA-N
• INCHI: 1S/C25H29F2N9O3/c26-16-9-30-23-20(22(28)32-36(23)12-16)24(37)31-19-11-29-10-18(27)21(19)34-3-1-15(2-4-34)25(38)35-7-5-33(6-8-35)17-13-39-14-17/h9-12,15,17H,1-8,13-14H2,(H2,28,32)(H,31,37)
• Isomeric SMILES: C1CN(CCC1C(=O)N2CCN(CC2)C3COC3)C4=C(C=NC=C4NC(=O)C5=C6N=CC(=CN6N=C5N)F)F
• PubChem CID: 86720912
• Molecular Weight: 541.55

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Pyrazolopyrimidines
      • Subclass Pyrazolo[1,5-a]pyrimidines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Pyrazolopyrimidines
• Subclass: Pyrazolo[1,5-a]pyrimidines
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyrazolo[1,5-a]pyrimidines
• Alternative Parents: Piperidinecarboxamides Pyrimidinecarboxamides Dialkylarylamines Pyrazole-4-carboxamides Aminopyridines and derivatives Halopyrimidines N-alkylpiperazines Aryl fluorides Imidolactams Tertiary carboxylic acid amides Vinylogous amides Heteroaromatic compounds Trialkylamines Secondary carboxylic acid amides Amino acids and derivatives Oxetanes Azacyclic compounds Dialkyl ethers Oxacyclic compounds Primary amines Carbonyl compounds Hydrocarbon derivatives Organofluorides Organic oxides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Pyrazolo[1,5-a]pyrimidine - Piperidinecarboxamide - Pyrimidinecarboxamide - Pyrazole-4-carboxamide - Tertiary aliphatic/aromatic amine - Dialkylarylamine - Aminopyridine - Halopyrimidine - N-alkylpiperazine - Aryl fluoride - Aryl halide - 1,4-diazinane - Piperazine - Piperidine - Pyridine - Pyrimidine - Imidolactam - Azole - Pyrazole - Vinylogous amide - Tertiary carboxylic acid amide - Heteroaromatic compound - Secondary carboxylic acid amide - Amino acid or derivatives - Tertiary aliphatic amine - Oxetane - Tertiary amine - Carboxamide group - Azacycle - Oxacycle - Carboxylic acid derivative - Dialkyl ether - Ether - Hydrocarbon derivative - Organic nitrogen compound - Organic oxygen compound - Organohalogen compound - Organofluoride - Organonitrogen compound - Organooxygen compound - Organic oxide - Amine - Carbonyl group - Primary amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as pyrazolo[1,5-a]pyrimidines. These are aromatic heterocyclic compounds containing a pyrazolo[3,4-d]pyrimidine ring system, which consists of a pyrazole ring fused to and sharing exactly one nitrogen atom with a pyrimidine ring.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

ATR Tchem Serine/threonine-protein kinase ATR (0 Activities)

Discover Target: ATR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Mechanisms of Action

Chemical and Physical Properties

• DMSO(mg / mL) Max Solubility: 15
• DMSO(mM) Max Solubility: 27.6982734742868
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 541.600 g/mol
• XLogP3: 0.100
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 5
• Exact Mass: 541.236 Da
• Monoisotopic Mass: 541.236 Da
• Topological Polar Surface Area: 134.000 Ų
• Heavy Atom Count: 39
• Formal Charge: 0
• Complexity: 885.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1