AZD1390 - Moligand™, ≥97% , Inhibitor of ATM serine/threonine kinase, CAS No.2089288-03-7, Inhibitor of ATM serine/threonine kinase

CAS: 2089288-03-7 Cat. No.: A414112 Peso molecular: 477.57

GRADE & PURITY Moligand™, ≥97%

Synonyms

C27H32FN5O2 | CI43QFE22O | GTPL11277 | CCG-269518 | AC-36283 | A16798 | 7-fluoro-1-isopropyl-3-methyl-8-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one | s8680 | D80599 | UNII-CI43QFE22O | 7-fluoro-3-methyl-8-[6-(3-piperidi

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

Information

AZD1390 is a first-in-class orally available and CNS penetrantATMinhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases.

Targets

ATM (Cell-based assay) 0.78 nM

In vitro

AZD1390 blocks ATM-dependent DDR (DNA damage response) pathway activity and combines with radiation to induce G2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. AZD1390 results in increased genome instability.

In vivo

AZD1390 displays excellent oral bioavailability in preclinical species (66% in rat and 74% in dog). It can efficiently cross the BBB in non-human primate PET studies. Profound tumor regressions and increased animal survival (>50 days) have been observed in orthotopic xenograft models of brain cancer following just 2 or 4 days combination treatment of AZD1390 with radiotherapy, compared to radiotherapy treatment alone. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induces tumor regressions and increased animal survival compared to IR treatment alone. AZD1390 has favorable physical, chemical, PK, and PD properties suitable for clinical applications that require exposures within the central nervous system.

Cell Research(from reference)

Cell lines：NCI-H2228 cells 

Concentrations：0-1250 nM 

Incubation Time：1 h 

Specifications

Sinónimos

C27H32FN5O2 | CI43QFE22O | GTPL11277 | CCG-269518 | AC-36283 | A16798 | 7-fluoro-1-isopropyl-3-methyl-8-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-1H-imidazo[4, 5-c]quinolin-2(3H)-one | s8680 | D80599 | UNII-CI43QFE22O | 7-fluoro-3-methyl-8-[6-(3-piperidi

Especificaciones y pureza

Moligand™, ≥97%

Mecanismos bioquímicos y fisiológicos

AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10, 000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kina

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 ATM serine/threonine kinase

Pureza

≥97%

Propiedades del producto

• ALogP: 4.231
• hba_count: 4
• Enlace rotable: 7

Nombres e identificadores

• Pubchem Sid: 504773016
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504773016
• Sonrisas canónicas: CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C
• IUPAC Name: 7-fluoro-3-methyl-8-[6-(3-piperidin-1-ylpropoxy)pyridin-3-yl]-1-propan-2-ylimidazo[4,5-c]quinolin-2-one
• InChIKey: VQSZIPCGAGVRRP-UHFFFAOYSA-N
• INCHI: 1S/C27H32FN5O2/c1-18(2)33-26-21-14-20(22(28)15-23(21)29-17-24(26)31(3)27(33)34)19-8-9-25(30-16-19)35-13-7-12-32-10-5-4-6-11-32/h8-9,14-18H,4-7,10-13H2,1-3H3
• Isómeros SMILES: CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C
• Peso molecular: 477.57
• Reaxy-Rn: 31033040
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=31033040&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Clase Quinolines and derivatives
      • Subclass Imidazoquinolines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Clase: Quinolines and derivatives
• Subclass: Imidazoquinolines
• Intermediate Tree Nodes: Not available
• Direct Parent: Imidazoquinolines
• Alternative Parents: Haloquinolines Imidazo-[4,5-c]pyridines Pyridinones Alkyl aryl ethers Piperidines N-substituted imidazoles Benzenoids Aryl fluorides Heteroaromatic compounds Ureas Trialkylamines Azacyclic compounds Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Imidazoquinoline - Haloquinoline - Imidazo-[4,5-c]pyridine - Imidazopyridine - Pyridinone - Alkyl aryl ether - Benzenoid - Pyridine - Piperidine - N-substituted imidazole - Aryl halide - Aryl fluoride - Heteroaromatic compound - Imidazole - Azole - Urea - Tertiary aliphatic amine - Tertiary amine - Azacycle - Ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Aromatic heteropolycyclic compound
• Descripción: This compound belongs to the class of organic compounds known as imidazoquinolines. These are aromatic heterocyclic compounds containing an imidazole ring fused to a quinoline ring system. In some configurations, the imidazole ring shares a nitrogen atom with the quinoline moiety.
• 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)

ATM Tchem Serine-protein kinase ATM (1 Activities)

Discover Target: ATM

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

KCNH2 Tclin Potassium voltage-gated channel subfamily H member 2 (1 Activities)

Discover Target: KCNH2

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

KCNH2 Tclin HERG (29587 Activities)

Discover Target: KCNH2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MTOR Tclin Serine/threonine-protein kinase mTOR (13850 Activities)

Discover Target: MTOR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SGK1 Tchem Serine/threonine-protein kinase Sgk1 (2343 Activities)

Discover Target: SGK1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CSF1R Tclin Macrophage colony stimulating factor receptor (5179 Activities)

Discover Target: CSF1R

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

ATM Tchem Serine-protein kinase ATM (4198 Activities)

Discover Target: ATM

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

ATR Tchem Serine-protein kinase ATR (986 Activities)

Discover Target: ATR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HT-29 (80576 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mecanismos de acción

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro Ethanol: 95 mg/mL (198.92 mM); DMSO: 14 mg/mL (29.31 mM); Water: Insoluble
• DMSO (mg/ml) Solubilidad máxima: 14
• DMSO (mM) Solubilidad máxima: 29.3150742299558
• Agua (mg/ml) Solubilidad máxima: ＜1
• Peso molecular: 477.600 g/mol
• XLogP3: 4.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 7
• Exact Mass: 477.254 Da
• Monoisotopic Mass: 477.254 Da
• Topological Polar Surface Area: 61.800 Ų
• Heavy Atom Count: 35
• Formal Charge: 0
• Complexity: 720.000
• 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