NMS-P118 - ≥97% , CAS No.1262417-51-5

CAS: 1262417-51-5 Cat. No.: N413987 Peso molecular: 395.42

GRADE & PURITY ≥97%

Synonyms

1H-Isoindole-4-carboxamide, 2-(1-(4,4-difluorocyclohexyl)-4-piperidinyl)-6-fluoro-2,3-dihydro-3-oxo- | AT32155 | EX-A1271 | 2-[1-(4,4-Difluorocyclohexyl)-piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide | 2-[1-(4,4-difluorocyclohexyl)

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

Information

NMS-P118 is a potent, orally available, and highly selectivePARP-1inhibitor endowed with excellent ADME and pharmacokinetic profiles, showing 150-fold selectivity for PARP-1 over PARP-2 (Kd 0.009 μM vs 1.39 μM, respectively).

Targets

PARP1 (Cell-free assay) 0.009 μM(Kd)

In vitro

NMS-P118 is a potent (KD = 0.009 μM) PARP-1 inhibitor, showing 150-fold selectivity over PARP-2 (KD = 1.39 μM). The compound shows high solubility and permeability.

In vivo

NMS-P118 is proved to be metabolically stable, it modestly inhibits two cytochrome P450 family members (CYP-2B6 IC50, 8.15 μM; CYP-2D6 IC50, 9.51 μM) out of eight isoforms tested. NMS-P118 has low in vivo clearance, and complete oral bioavailability. The pharmacokinetic profile of NMS-P118 in rat dosed iv at 10 mg/kg and orally at 10 and 100 mg/kg, mirrors that observed in the mouse, with oral bioavailability >65%, and linearity of exposure with dose. Its treatment dramatically decreases intratumoral PAR levels at 1, 2, and 6 h after administration and partial recovery of PAR levels is observed at 24 h. NMS-P118 shows excellent ADME and pharmacokinetic profiles, high oral availability in the mouse and rat, and high efficacy both as a single agent and in combination with Temozolomide in BRCA1-mutated MDA-MB-436 and BRCA2 deficient Capan-1 human tumor xenograft models, respectively.

Cell Research(from reference)

Cell lines：HeLa cells 

Incubation Time：30 mins 

Specifications

Sinónimos

1H-Isoindole-4-carboxamide, 2-(1-(4, 4-difluorocyclohexyl)-4-piperidinyl)-6-fluoro-2, 3-dihydro-3-oxo- | AT32155 | EX-A1271 | 2-[1-(4, 4-Difluorocyclohexyl)-piperidin-4-yl]-6-fluoro-3-oxo-2, 3-dihydro-1H-isoindole-4-carboxamide | 2-[1-(4, 4-difluorocyclohexyl)

Especificaciones y pureza

≥97%

Mecanismos bioquímicos y fisiológicos

NMS-P118 is a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles, showing 150-fold selectivity for PARP-1 over PARP-2 (Kd 0.009 μM vs 1.39 μM, respectively).

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.

Tipo de acción

INHIBITOR

Pureza

≥97%

Nombres e identificadores

• Pubchem Sid: 488201439
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/488201439
• Sonrisas canónicas: C1CC(CCC1N2CCC(CC2)N3CC4=C(C3=O)C(=CC(=C4)F)C(=O)N)(F)F
• IUPAC Name: 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-1H-isoindole-4-carboxamide
• InChIKey: ARYVAQSYRLZVQD-UHFFFAOYSA-N
• INCHI: 1S/C20H24F3N3O2/c21-13-9-12-11-26(19(28)17(12)16(10-13)18(24)27)15-3-7-25(8-4-15)14-1-5-20(22,23)6-2-14/h9-10,14-15H,1-8,11H2,(H2,24,27)
• Isómeros SMILES: C1CC(CCC1N2CCC(CC2)N3CC4=C(C3=O)C(=CC(=C4)F)C(=O)N)(F)F
• Peso molecular: 395.42
• Reaxy-Rn: 21181864
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=21181864&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Clase Isoindoles and derivatives
      • Subclass Isoindolines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Clase: Isoindoles and derivatives
• Subclass: Isoindolines
• Intermediate Tree Nodes: Not available
• Direct Parent: Isoindolones
• Alternative Parents: Isoindoles Cyclohexyl halides Cyclohexylamines Aryl fluorides Benzenoids Piperidines Tertiary carboxylic acid amides Amino acids and derivatives Trialkylamines Primary carboxylic acid amides Lactams Azacyclic compounds Organooxygen compounds Organopnictogen compounds Alkyl fluorides Hydrocarbon derivatives Organofluorides Organic oxides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Isoindolone - Isoindole - Cyclohexylamine - Cyclohexyl halide - Aryl fluoride - Aryl halide - Piperidine - Benzenoid - Tertiary carboxylic acid amide - Amino acid or derivatives - Carboxamide group - Lactam - Primary carboxylic acid amide - Tertiary amine - Tertiary aliphatic amine - Carboxylic acid derivative - Azacycle - Organofluoride - Organohalogen compound - Amine - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Alkyl halide - Organic oxygen compound - Organonitrogen compound - Organooxygen compound - Alkyl fluoride - Organic nitrogen compound - Aromatic heteropolycyclic compound
• Descripción: This compound belongs to the class of organic compounds known as isoindolones. These are aromatic polycyclic compounds that an isoindole bearing a ketone.
• 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)

PARP1 Tclin Poly [ADP-ribose] polymerase 1 (3 Activities)

Discover Target: PARP1

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

ABL1 Tclin Tyrosine-protein kinase ABL (18331 Activities)

Discover Target: ABL1

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

EGFR Tclin Epidermal growth factor receptor erbB1 (33727 Activities)

Discover Target: EGFR

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

INSR Tclin Insulin receptor (5558 Activities)

Discover Target: INSR

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

PDGFRB Tclin Platelet-derived growth factor receptor beta (5195 Activities)

Discover Target: PDGFRB

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

KIT Tclin Stem cell growth factor receptor (10667 Activities)

Discover Target: KIT

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

LCK Tclin Tyrosine-protein kinase LCK (9212 Activities)

Discover Target: LCK

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

MAPK14 Tchem MAP kinase p38 alpha (12866 Activities)

Discover Target: MAPK14

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

GSK3B Tclin Glycogen synthase kinase-3 beta (11785 Activities)

Discover Target: GSK3B

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

FGFR1 Tclin Fibroblast growth factor receptor 1 (9149 Activities)

Discover Target: FGFR1

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

PDPK1 Tchem 3-phosphoinositide dependent protein kinase-1 (3758 Activities)

Discover Target: PDPK1

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

IKBKB Tchem Inhibitor of nuclear factor kappa B kinase beta subunit (5554 Activities)

Discover Target: IKBKB

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

AURKB Tchem Serine/threonine-protein kinase Aurora-B (6805 Activities)

Discover Target: AURKB

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

PIM1 Tchem Serine/threonine-protein kinase PIM1 (9629 Activities)

Discover Target: PIM1

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

JAK3 Tclin Tyrosine-protein kinase JAK3 (8349 Activities)

Discover Target: JAK3

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

SYK Tclin Tyrosine-protein kinase SYK (7372 Activities)

Discover Target: SYK

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

PLK1 Tchem Serine/threonine-protein kinase PLK1 (28605 Activities)

Discover Target: PLK1

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

JAK1 Tclin Tyrosine-protein kinase JAK1 (8569 Activities)

Discover Target: JAK1

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

JAK2 Tclin Tyrosine-protein kinase JAK2 (12915 Activities)

Discover Target: JAK2

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

KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)

Discover Target: KDR

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

MAPKAPK2 Tchem MAP kinase-activated protein kinase 2 (4814 Activities)

Discover Target: MAPKAPK2

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

PTK2 Tclin Focal adhesion kinase 1 (4730 Activities)

Discover Target: PTK2

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

CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)

Discover Target: CYP2D6

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

MET Tclin Hepatocyte growth factor receptor (10718 Activities)

Discover Target: MET

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

PARP1 Tclin Poly [ADP-ribose] polymerase-1 (6206 Activities)

Discover Target: PARP1

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

LYN Tclin Tyrosine-protein kinase Lyn (4251 Activities)

Discover Target: LYN

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

NTRK1 Tclin Nerve growth factor receptor Trk-A (7922 Activities)

Discover Target: NTRK1

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

PRKACA Tchem cAMP-dependent protein kinase alpha-catalytic subunit (3475 Activities)

Discover Target: PRKACA

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

ZAP70 Tchem Tyrosine-protein kinase ZAP-70 (2189 Activities)

Discover Target: ZAP70

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

AKT1 Tchem Serine/threonine-protein kinase AKT (9192 Activities)

Discover Target: AKT1

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

FLT3 Tclin Tyrosine-protein kinase receptor FLT3 (13481 Activities)

Discover Target: FLT3

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

TYK2 Tclin Tyrosine-protein kinase TYK2 (5029 Activities)

Discover Target: TYK2

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

CHEK1 Tchem Serine/threonine-protein kinase Chk1 (6846 Activities)

Discover Target: CHEK1

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

AURKA Tchem Serine/threonine-protein kinase Aurora-A (10240 Activities)

Discover Target: AURKA

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

EEF2K Tchem Serine/threonine-protein kinase EEF2K (1246 Activities)

Discover Target: EEF2K

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

CYP2B6 Tchem Cytochrome P450 2B6 (1338 Activities)

Discover Target: CYP2B6

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

EPHA2 Tclin Ephrin type-A receptor 2 (3499 Activities)

Discover Target: EPHA2

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

TTK Tchem Dual specificity protein kinase TTK (2978 Activities)

Discover Target: TTK

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

TNK2 Tclin Tyrosine kinase non-receptor protein 2 (2836 Activities)

Discover Target: TNK2

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

PTK6 Tchem Tyrosine-protein kinase BRK (2605 Activities)

Discover Target: PTK6

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

MKNK2 Tchem MAP kinase signal-integrating kinase 2 (3518 Activities)

Discover Target: MKNK2

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

NEK6 Tchem Serine/threonine-protein kinase NEK6 (1986 Activities)

Discover Target: NEK6

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

PIM2 Tchem Serine/threonine-protein kinase PIM2 (5873 Activities)

Discover Target: PIM2

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

DLD-1 (17511 Activities)

Explore this target

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

MCF7 (126967 Activities)

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

RET Tclin Tyrosine-protein kinase receptor RET (6732 Activities)

Discover Target: RET

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

PAK4 Tchem Serine/threonine-protein kinase PAK 4 (3212 Activities)

Discover Target: PAK4

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

ALK Tclin ALK tyrosine kinase receptor (7132 Activities)

Discover Target: ALK

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

NIM1K Tchem Serine/threonine-protein kinase NIM1 (270 Activities)

Discover Target: NIM1K

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

MELK Tchem Maternal embryonic leucine zipper kinase (3491 Activities)

Discover Target: MELK

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

PARP2 Tclin Poly [ADP-ribose] polymerase 2 (1185 Activities)

Discover Target: PARP2

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

Objetivos asociados (no humanos)

Prkcb Protein kinase C beta (2 Activities)

Discover Target: Prkcb

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

Mapk1 MAP kinase ERK2 (650 Activities)

Discover Target: Mapk1

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

Mus musculus (284745 Activities)

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

Rattus norvegicus (775804 Activities)

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

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

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

Liver microsome (341 Activities)

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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 DMSO: 79 mg/mL warmed with 50ºC Water: bath (199.78 mM); Ethanol: 10 mg/mL warmed with 50ºC Water: bath (25.28 mM); Water: Insoluble
• Peso molecular: 395.400 g/mol
• XLogP3: 2.500
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 395.182 Da
• Monoisotopic Mass: 395.182 Da
• Topological Polar Surface Area: 66.600 Ų
• Heavy Atom Count: 28
• Formal Charge: 0
• Complexity: 614.000
• 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