Nemiralisib (GSK2269557) - Moligand™, ≥99% , PI3-kinase p110-delta subunit inhibitor, CAS No.1254036-71-9, PI3-kinase p110-delta subunit inhibitor

CAS: 1254036-71-9 Cat. No.: N413878 Molecular Weight: 440.54 EC Number: 689-356-1

GRADE & PURITY Moligand™, ≥99%

Synonyms

6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazole | FT-0716060 | GSK2269557 free base | GSK-2269557 free base | 1254036-71-9 | GSK2269557A | GSK-2269557A | SCHEMBL109919 | EX-A5754 | VVX | BBL011727 | MS-27918 |

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

Nemiralisib, also known as GSK-2269557, is a potent and selectivePI3Kδinhibitor(pKi = 9.9).

Targets

PI3Kδ (Cell-free assay) 9.9(pKi)

In vivo

GSK-2269557 has low oral bioavailability (F=2%) and in vivo clearance of 28 mL/min/kg but has a high volume of distribution of 6.3 L/kg. GSK-2269557 induces concentration-dependent increases in QT interval and T_p-e at 0.3 and 1 μM (1 and 0.5 Hz) and an increase in QRS at 1 μM (2 Hz), however, no treatment-related torsades de pointes (TdP) arrhythmias are observed. In a disease relevant brown Norway rat acute OVA model of Th2 driven lung inflammation, GSK-2269557 is shown to protect against eosinophil recruitment with an ED50 of 67 μg/kg and dose-dependently reduces recruitment of all leukocyte subpopulations and IL-13 in the lungs.

Specifications

Synonyms

6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1, 3-oxazol-2-yl)-1H-indazole | FT-0716060 | GSK2269557 free base | GSK-2269557 free base | 1254036-71-9 | GSK2269557A | GSK-2269557A | SCHEMBL109919 | EX-A5754 | VVX | BBL011727 | MS-27918 |

Specifications & Purity

Moligand™, ≥99%

Biochemical and Physiological Mechanisms

Nemiralisib, also known as GSK-2269557, is a potent and selective PI3Kδ inhibitor(pKi = 9.9).

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

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

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

PI3-kinase p110-delta subunit inhibitor

Purity

≥99%

Product Properties

• ALogP: 3.943
• hba_count: 3
• HBD Count: 2
• Rotatable Bond: 5

Names and Identifiers

• Pubchem Sid: 504770925
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504770925
• Canonical Smiles: CC(C)N1CCN(CC1)CC2=CN=C(O2)C3=C4C=NNC4=CC(=C3)C5=C6C=CNC6=CC=C5
• IUPAC Name: 2-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole
• InChIKey: MCIDWGZGWVSZMK-UHFFFAOYSA-N
• INCHI: 1S/C26H28N6O/c1-17(2)32-10-8-31(9-11-32)16-19-14-28-26(33-19)22-12-18(13-25-23(22)15-29-30-25)20-4-3-5-24-21(20)6-7-27-24/h3-7,12-15,17,27H,8-11,16H2,1-2H3,(H,29,30)
• Isomeric SMILES: CC(C)N1CCN(CC1)CC2=CN=C(O2)C3=C4C=NNC4=CC(=C3)C5=C6C=CNC6=CC=C5
• Molecular Weight: 440.54
• Reaxy-Rn: 20834272
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=20834272&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Benzopyrazoles
      • Subclass Indazoles

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Benzopyrazoles
• Subclass: Indazoles
• Intermediate Tree Nodes: Not available
• Direct Parent: Indazoles
• Alternative Parents: Indoles N-alkylpiperazines Aralkylamines 2,5-disubstituted oxazoles Benzenoids Pyrroles Pyrazoles Heteroaromatic compounds Trialkylamines Oxacyclic compounds Azacyclic compounds Organooxygen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Benzopyrazole - Indazole - Indole - Indole or derivatives - 2,5-disubstituted 1,3-oxazole - N-alkylpiperazine - Aralkylamine - Benzenoid - Piperazine - 1,4-diazinane - Pyrrole - Pyrazole - Oxazole - Azole - Heteroaromatic compound - Tertiary aliphatic amine - Tertiary amine - Oxacycle - Azacycle - Amine - Organic oxygen compound - Hydrocarbon derivative - Organic nitrogen compound - Organonitrogen compound - Organooxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as indazoles. These are compounds containing an indazole, which is structurally characterized by a pyrazole fused to a benzene.
• 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)

PIK3CG Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (1 Activities)

Discover Target: PIK3CG

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

PIK3CA Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (1 Activities)

Discover Target: PIK3CA

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

PIK3CB Tchem Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (1 Activities)

Discover Target: PIK3CB

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

PIK3CD Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (2 Activities)

Discover Target: PIK3CD

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)

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

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

CSNK1D Tchem Casein kinase I delta (4546 Activities)

Discover Target: CSNK1D

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

PIK3CD Tclin PI3-kinase p110-delta subunit (6699 Activities)

Discover Target: PIK3CD

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

CDK2 Tchem Cyclin-dependent kinase 2 (9050 Activities)

Discover Target: CDK2

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

PIK3CG Tclin PI3-kinase p110-gamma subunit (5411 Activities)

Discover Target: PIK3CG

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

PIK3CB Tchem PI3-kinase p110-beta subunit (4044 Activities)

Discover Target: PIK3CB

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

U2OS (164939 Activities)

Explore this target

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

HepG2 (196354 Activities)

Explore this target

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

BRD4 Tchem Bromodomain-containing protein 4 (13122 Activities)

Discover Target: BRD4

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

TRIM24 Tchem Transcription intermediary factor 1-alpha (2087 Activities)

Discover Target: TRIM24

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

BRPF1 Tchem Peregrin (2217 Activities)

Discover Target: BRPF1

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

HEK-293T (167025 Activities)

Explore this target

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

Associated Targets(non-human)

PIK3CA PI3-kinase p110-alpha subunit (51 Activities)

Discover Target: PIK3CA

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

Fgfr3 Fibroblast growth factor receptor 3 (21 Activities)

Discover Target: Fgfr3

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

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 88 mg/mL (199.75 mM); Ethanol: 8 mg/mL (18.15 mM); Water: Insoluble
• DMSO(mg / mL) Max Solubility: 88
• DMSO(mM) Max Solubility: 199.7548463
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 440.500 g/mol
• XLogP3: 3.900
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 5
• Exact Mass: 440.232 Da
• Monoisotopic Mass: 440.232 Da
• Topological Polar Surface Area: 77.000 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 655.000
• 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