GRADE & PURITY 10mM in DMSO

Synonyms

5-(6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

GNE-317 GNE-317 is a potent, brain-penetrant PI3K inhibitor.

Targets

PI3K

In vitro

GNE-317 is not a substrate of P-gp or BCRP transporter in transfected Madin-Darby canine kidney (MDCK) cells. Binding of GNE-317 to plasma proteins exhibits a free fraction of 14.9 % in mouse plasma, and binding to brain tissues is higher, with a free fraction of 5.4%. GNE-317 shows cytostasis but no cell death to U87 cells.

In vivo

GNE-317 (40 mg/kg, p.o.) markedly inhibits the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 (40 mg/kg, p.o.) is efficacious in the U87 and GS2 orthotopic models, achieving tumor growth inhibition of 90% and 50%, respectively. In the GBM10 tumor model, GNE-317 (30 mg/kg, p.o.; 40 mg/kg the first 2 weeks) extends the survival of mice from a median of 55.5 to 75 days.

Specifications

Synonyms

5-(6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholinothieno[3, 2-d]pyrimidin-2-yl)pyrimidin-2-amine

Specifications & Purity

10mM in DMSO

Biochemical and Physiological Mechanisms

GNE-317 is a potent, brain-penetrant PI3K inhibitor.

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.

Action Type

INHIBITOR

Product Properties

• ALogP: 1.5
• hba_count: 7
• HBD Count: 1
• Rotatable Bond: 4

Names and Identifiers

• Canonical Smiles: CC1=C(SC2=C1N=C(N=C2N3CCOCC3)C4=CN=C(N=C4)N)C5(COC5)OC
• IUPAC Name: 5-[6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine
• InChIKey: XOZLHJMDLKDZAL-UHFFFAOYSA-N
• INCHI: 1S/C19H22N6O3S/c1-11-13-14(29-15(11)19(26-2)9-28-10-19)17(25-3-5-27-6-4-25)24-16(23-13)12-7-21-18(20)22-8-12/h7-8H,3-6,9-10H2,1-2H3,(H2,20,21,22)
• Isomeric SMILES: CC1=C(SC2=C1N=C(N=C2N3CCOCC3)C4=CN=C(N=C4)N)C5(COC5)OC
• Molecular Weight: 414.48
• Reaxy-Rn: 23003622
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=23003622&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Diazines
      • Subclass Pyrimidines and pyrimidine derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Diazines
• Subclass: Pyrimidines and pyrimidine derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Bipyrimidines and oligopyrimidines
• Alternative Parents: Thienopyrimidines Dialkylarylamines Aminopyrimidines and derivatives Morpholines Imidolactams Thiophenes Heteroaromatic compounds Oxetanes Oxacyclic compounds Dialkyl ethers Azacyclic compounds Primary amines Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Bipyrimidine - Thienopyrimidine - Dialkylarylamine - Aminopyrimidine - Morpholine - Oxazinane - Imidolactam - Heteroaromatic compound - Thiophene - Oxetane - Dialkyl ether - Ether - Oxacycle - Azacycle - Organonitrogen compound - Hydrocarbon derivative - Organic nitrogen compound - Amine - Organooxygen compound - Organic oxygen compound - Primary amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as bipyrimidines and oligopyrimidines. These are organic compounds containing two or more pyrimidine rings directly linked to each other. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
• 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)

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)

MTOR Tclin Serine/threonine-protein kinase mTOR (2 Activities)

Discover Target: MTOR

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

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

SF-268 (49410 Activities)

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

SF-539 (44845 Activities)

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

PIK3C2B Tchem Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide (438 Activities)

Discover Target: PIK3C2B

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

Mus musculus (284745 Activities)

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

Brain (1 Activities)

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

Plasma (328 Activities)

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

Mechanisms of Action

Chemical and Physical Properties

• DMSO(mg / mL) Max Solubility: 47
• DMSO(mM) Max Solubility: 113.3950975
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 414.500 g/mol
• XLogP3: 0.500
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 4
• Exact Mass: 414.147 Da
• Monoisotopic Mass: 414.147 Da
• Topological Polar Surface Area: 137.000 Ų
• Heavy Atom Count: 29
• Formal Charge: 0
• Complexity: 570.000
• 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