GRADE & PURITY ≥98%

Synonyms

5H-​Pyrazolo[4,​3-​c]​pyridine-​5-​carboxamide,3-​[7-​(difluoromethyl)​-​3,​4-​dihydro-​6-​(1-​methyl-​1H-​pyrazol-​4-​yl)​-​1(2H)​-​quinolinyl]​-​1,​4,​6,​7-​tetrahydro-​N-​methyl-​1-​(tetrahydro-​2H-​pyran-​4-​yl)​-

Storage

Store at -20°C,Argon charged

Shipped In

Ice chest + Ice pads

Overview

Information

GNE-781 GNE-781 (compound 19) is an orally active, highly potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein (CBP) with IC50 of 0.94 nM in TR-FRET assay. GNE-781 also inhibits BRET and BRD4(1) with IC50 of 6.2 nM and 5100 nM, respectively. GNE-781 exhibits antitumor activity.

Targets

CBP (in TR-FRET assay); BRET (Cell-free assay); BRD4(1) (Cell-free assay) 0.94 nM; 6.2 nM; 5100 nM

In vitro

In vitro studies show that GNE-781 reduces FOXP3 (forkhead box P3) transcript levels with a less optimal chemical probe, suggesting that inhibition of the CBP bromodomain may provide a novel small molecule therapeutic approach for cancer immunotherapy. GNE-781 decreases the generation of iTregs in vitro without affecting cell viability.

In vivo

GNE-781, a highly potent and selective CBP inhibitor that is efficacious in a MOLM-16 AML xenograft model. GNE-781 modulates MYC expression that corresponds with antitumor activity in an AML tumor model.

Cell Research(from reference)

Cell lines：MV-4-11 

Concentrations：0.002-12.7 μM 

Incubation Time：4 h 

Specifications

Synonyms

5H-​Pyrazolo[4, ​3-​c]​pyridine-​5-​carboxamide, 3-​[7-​(difluoromethyl)​-​3, ​4-​dihydro-​6-​(1-​methyl-​1H-​pyrazol-​4-​yl)​-​1(2H)​-​quinolinyl]​-​1, ​4, ​6, ​7-​tetrahydro-​N-​methyl-​1-​(tetrahydro-​2H-​pyran-​4-​yl)​-

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

GNE-781 (compound 19) is an orally active, highly potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein (CBP) with IC50 of 0.94 nM in TR-FRET assay. GNE-781 also inhibits BRET and BRD4(1) with IC50 o

Storage

Store at -20°C, Argon charged

Shipped In

Ice chest + Ice pads

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

Action Type

INHIBITOR

Purity

≥98%

Names and Identifiers

• Canonical Smiles: CNC(=O)N1CCC2=C(C1)C(=NN2C3CCOCC3)N4CCCC5=CC(=C(C=C54)C(F)F)C6=CN(N=C6)C
• IUPAC Name: 3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-N-methyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide
• InChIKey: CQCWHSDMJBAGDC-UHFFFAOYSA-N
• INCHI: 1S/C27H33F2N7O2/c1-30-27(37)34-9-5-23-22(16-34)26(32-36(23)19-6-10-38-11-7-19)35-8-3-4-17-12-20(18-14-31-33(2)15-18)21(25(28)29)13-24(17)35/h12-15,19,25H,3-11,16H2,1-2H3,(H,30,37)
• Isomeric SMILES: CNC(=O)N1CCC2=C(C1)C(=NN2C3CCOCC3)N4CCCC5=CC(=C(C=C54)C(F)F)C6=CN(N=C6)C
• Molecular Weight: 525.59
• Reaxy-Rn: 29684228
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=29684228&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic nitrogen compounds
    • Class Organonitrogen compounds
      • Subclass Amines
        • Level5 Tertiary amines
          • Level6 Tertiary alkylarylamines
            • Level7 Alkyldiarylamines

• Kingdom: Organic compounds
• Superclass: Organic nitrogen compounds
• Class: Organonitrogen compounds
• Subclass: Amines
• Intermediate Tree Nodes: Tertiary amines - Tertiary alkylarylamines
• Direct Parent: Alkyldiarylamines
• Alternative Parents: Hydroquinolines Pyridinecarboxamides Oxanes Imidolactams Benzenoids Pyrazoles Heteroaromatic compounds Ureas Oxacyclic compounds Dialkyl ethers Azacyclic compounds Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives Carbonyl compounds Alkyl fluorides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Alkyldiarylamine - Tetrahydroquinoline - Pyridinecarboxamide - Imidolactam - Benzenoid - Oxane - Heteroaromatic compound - Pyrazole - Azole - Urea - Carbonic acid derivative - Oxacycle - Azacycle - Organoheterocyclic compound - Ether - Dialkyl ether - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organofluoride - Organohalogen compound - Carbonyl group - Alkyl halide - Alkyl fluoride - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as alkyldiarylamines. These are tertiary alkylarylamines having two aryl and one alkyl groups attached to the amino 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

Associated Targets(Human)

EP300 Tchem Histone acetyltransferase p300 (1 Activities)

Discover Target: EP300

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

CREBBP Tchem CREB-binding protein (4 Activities)

Discover Target: CREBBP

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

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

CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)

Discover Target: CYP1A2

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

CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)

Discover Target: CYP2C9

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

CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)

Discover Target: CYP2C19

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

CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)

Discover Target: CYP3A4

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

EP300 Tchem Histone acetyltransferase p300 (1259 Activities)

Discover Target: EP300

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

KAT2B Tchem Histone acetyltransferase PCAF (884 Activities)

Discover Target: KAT2B

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

CREBBP Tchem CREB-binding protein (1602 Activities)

Discover Target: CREBBP

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

BAZ2B Tchem Bromodomain adjacent to zinc finger domain protein 2B (56204 Activities)

Discover Target: BAZ2B

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

BPTF Tchem Nucleosome-remodeling factor subunit BPTF (194 Activities)

Discover Target: BPTF

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

CECR2 Tchem Cat eye syndrome critical region protein 2 (340 Activities)

Discover Target: CECR2

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

BRD9 Tchem Bromodomain-containing protein 9 (684 Activities)

Discover Target: BRD9

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

TAF1 Tchem Transcription initiation factor TFIID subunit 1 (441 Activities)

Discover Target: TAF1

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

Associated Targets(non-human)

Canis familiaris (36305 Activities)

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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

Cynomolgus monkey (4946 Activities)

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

GCN5 Histone acetyltransferase GCN5 (89 Activities)

Discover Target: GCN5

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

Plasma (328 Activities)

Explore this target

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: 100 mg/mL (190.26 mM); Ethanol: 100 mg/mL (190.26 mM); Water: Insoluble
• Molecular Weight: 525.600 g/mol
• XLogP3: 2.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 525.266 Da
• Monoisotopic Mass: 525.266 Da
• Topological Polar Surface Area: 80.500 Ų
• Heavy Atom Count: 38
• Formal Charge: 0
• Complexity: 833.000
• 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