ARQ 531 - Moligand™, ≥98% , Inhibitor of BLK proto-oncogene; Src family tyrosine kinase;Inhibitor of BMX non-receptor tyrosine kinase;Inhibitor of Bruton tyrosine kinase;Inhibitor of tec protein tyrosine kinase;Inhibitor of YES proto-oncogene 1; Src famil, Inhibitor of BLK proto-oncogene; Src family tyrosine kinase;Inhibitor of BMX non-receptor tyrosine kinase;Inhibitor of Bruton tyrosine kinase;Inhibitor of tec protein tyrosine kinase;Inhibitor of YES proto-oncogene 1; Src family tyrosine kinase

CAS: 2095393-15-8 Cat. No.: A414128 Peso molecular: 478.93 Número EC: 880-144-6

GRADE & PURITY Moligand™, ≥98%

Synonyms

AS-79762 | (2-Chloro-4-phenoxyphenyl)(4-(((3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)amino)-7H-pyrrolo(2,3-d)pyrimidin-5-yl)methanone | 1,5-Anhydro-2-[[5-(2-chloro-4-phenoxybenzoyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2,3,4-trideoxy-D-erythro-he

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

Information

ARQ 531 ARQ 531 is an ATP-competitive tyrosine kinase inhibitor designed to target BTK with an IC50 of 0.85 nM. It also has a distinct kinase selectivity profile with strong inhibitory activity against several key oncogenic drivers from TEC, Trk and Src family kinases.

Targets

BTK (Cell-free assay); BRK (Cell-dree); BRK (Cell-free assay); LCK (Cell-free); LCK (Cell-free assay) 29927,0.85 nM; 2.45 nM; 2.45 nM; 3.86 nM; 3.86 nM

In vitro

ARQ 531 potently inhibited BTK (IC50 = 0.85 nM), the binding potency was accompanied by long residence time (51 min). ARQ 531 selectively inhibits BCR signaling dependent PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin pathways in TMD8 cells. It potently inhibits proliferation of hematological malignant cell lines both sensitive and resistant to ibrutinib addicted to BCR signaling. Unlike ibrutinib, ARQ 531 suppressed both the upstream activating signals (via inhibition of a select member of Src kinase family) and the downstream signaling pathways (via pAKT and pERK kinases). In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), ARQ 531 potently suppressed expression of anti-apoptotic c-Myc and BCL6 oncoproteins in a dose dependent fashion, and concomitantly induced apoptotic cleavage of PARP protein.

In vivo

ARQ 531 has potent anti-tumor activity was observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models. ARQ 531 crosses the blood, brain-barrier. In a single oral dose study of 10mg/kg in monkeys, the bioavailability of ARQ 531 is 72.4% with a Cmax of 9 μM and a half-life greater than 24 hours.

Cell Research(from reference)

Cell lines：CLL cells 

Concentrations：0.1 μM, 1.0 μM, or 10.0 μM 

Incubation Time：72 h 

Specifications

Sinónimos

AS-79762 | (2-Chloro-4-phenoxyphenyl)(4-(((3R, 6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)amino)-7H-pyrrolo(2, 3-d)pyrimidin-5-yl)methanone | 1, 5-Anhydro-2-[[5-(2-chloro-4-phenoxybenzoyl)-7H-pyrrolo[2, 3-d]pyrimidin-4-yl]amino]-2, 3, 4-trideoxy-D-erythro-he

Especificaciones y pureza

Moligand™, ≥98%

Mecanismos bioquímicos y fisiológicos

ARQ 531 is an ATP-competitive tyrosine kinase inhibitor designed to target BTK with an IC50 of 0.85 nM. It also has a distinct kinase selectivity profile with strong inhibitory activity against several key oncogenic drivers from TEC, Trk and Src family ki

Condiciones de almacenamiento de almacenamiento

Store at -20°C

Enviado en

Ice chest + Ice pads

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

Inhibitor of BLK proto-oncogene; Src family tyrosine kinase;Inhibitor of BMX non-receptor tyrosine kinase;Inhibitor of Bruton tyrosine kinase;Inhibitor of tec protein tyrosine kinase;Inhibitor of YES proto-oncogene 1; Src family tyrosine kinase

Pureza

≥98%

Propiedades del producto

• ALogP: 4.368
• hba_count: 5
• Recuento HBD: 3
• Enlace rotable: 7

Nombres e identificadores

• Pubchem Sid: 504773042
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504773042
• Sonrisas canónicas: C1CC(OCC1NC2=NC=NC3=C2C(=CN3)C(=O)C4=C(C=C(C=C4)OC5=CC=CC=C5)Cl)CO
• IUPAC Name: (2-chloro-4-phenoxyphenyl)-[4-[[(3R,6S)-6-(hydroxymethyl)oxan-3-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]methanone
• InChIKey: JSFCZQSJQXFJDS-QAPCUYQASA-N
• INCHI: 1S/C25H23ClN4O4/c26-21-10-17(34-16-4-2-1-3-5-16)8-9-19(21)23(32)20-11-27-24-22(20)25(29-14-28-24)30-15-6-7-18(12-31)33-13-15/h1-5,8-11,14-15,18,31H,6-7,12-13H2,(H2,27,28,29,30)/t15-,18+/m1/s1
• Isómeros SMILES: C1C[C@H](OC[C@@H]1NC2=NC=NC3=C2C(=CN3)C(=O)C4=C(C=C(C=C4)OC5=CC=CC=C5)Cl)CO
• Peso molecular: 478.93
• Reaxy-Rn: 38494443
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=38494443&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Clase Benzene and substituted derivatives
      • Subclass Diphenylethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Clase: Benzene and substituted derivatives
• Subclass: Diphenylethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diphenylethers
• Alternative Parents: Aryl-phenylketones Diarylethers Pyrrolo[2,3-d]pyrimidines Phenoxy compounds Phenol ethers Benzoyl derivatives Secondary alkylarylamines Chlorobenzenes Aminopyrimidines and derivatives Substituted pyrroles Oxanes Imidolactams Aryl chlorides Vinylogous halides Vinylogous amides Heteroaromatic compounds Oxacyclic compounds Dialkyl ethers Azacyclic compounds Primary alcohols Organopnictogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Aryl-phenylketone - Diphenylether - Diaryl ether - Pyrrolo[2,3-d]pyrimidine - Pyrrolopyrimidine - Phenoxy compound - Aryl ketone - Phenol ether - Benzoyl - Secondary aliphatic/aromatic amine - Halobenzene - Chlorobenzene - Aminopyrimidine - Imidolactam - Substituted pyrrole - Pyrimidine - Oxane - Aryl halide - Aryl chloride - Heteroaromatic compound - Vinylogous amide - Vinylogous halide - Pyrrole - Ketone - Oxacycle - Azacycle - Organoheterocyclic compound - Secondary amine - Ether - Dialkyl ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Primary alcohol - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Amine - Alcohol - Aromatic heteropolycyclic compound
• Descripción: This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
• 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

Objetivos asociados (humanos)

YES1 Tclin Tyrosine-protein kinase Yes (0 Activities)

Discover Target: YES1

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

TEC Tchem Tyrosine-protein kinase Tec (0 Activities)

Discover Target: TEC

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

BTK Tclin Tyrosine-protein kinase BTK (2 Activities)

Discover Target: BTK

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

BMX Tchem Cytoplasmic tyrosine-protein kinase BMX (0 Activities)

Discover Target: BMX

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

BLK Tchem Tyrosine-protein kinase Blk (0 Activities)

Discover Target: BLK

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

Mecanismos de acción

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro DMSO: 95 mg/mL (198.35 mM); Ethanol: 7 mg/mL (14.61 mM); Water: Insoluble
• DMSO (mg/ml) Solubilidad máxima: 95
• DMSO (mM) Solubilidad máxima: 198.358841584365
• Agua (mg/ml) Solubilidad máxima: ＜1
• Peso molecular: 478.900 g/mol
• XLogP3: 4.300
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 7
• Exact Mass: 478.141 Da
• Monoisotopic Mass: 478.141 Da
• Topological Polar Surface Area: 109.000 Ų
• Heavy Atom Count: 34
• Formal Charge: 0
• Complexity: 681.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 2
• 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