GNF-6231 - Moligand™, 10mM in DMSO , Inhibitor of porcupine O-acyltransferase, CAS No.1243245-18-2, Inhibitor of porcupine O-acyltransferase

CAS: 1243245-18-2 Cat. No.: G421042 Molecular Weight: 448.49

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

[2,​4'-​Bipyridine]​-​5-​acetamide,N-​[5-​(4-​acetyl-​1-​piperazinyl)​-​2-​pyridinyl]​-​2'-​fluoro-​3-​methyl-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

GNF-6231 GNF-6231 is a potent, orally active and selective Porcupine inhibitor with IC50 of 0.8 nM.

Targets

Porcupine (Cell-free) 0.8 nM

In vitro

GNF-6231 shows a good solubility. It has no appreciable activities, at least up to 10 μM testing concentrations, for more than 200 off-targets, which include GPCRs, kinases, proteases, transporters, ion channels, and nuclear receptors. GNF-6231 shows IC50s of greater than 10 μM on all CYP isoforms tested (2C9, 2D6, 3A4). It shows high permeability in a Caco-2 human cell permeability assay with a possible efflux.

In vivo

GNF-6231 demonstrates excellent pathway inhibition and induces robust antitumor efficacy in a mouse MMTV-WNT1 xenograft tumor model. GNF-6231 is moderately bound to mouse, rat, dog, monkey, and human plasma proteins (88.0, 83.1, 90.9, 71.2, and 95%, respectively). It shows good oral bioavailability, ranging from 72 to 96% in preclinical species (mouse, rat, and dog) when dosed in solution formulations. GNF-6231 is expected to have minimal to marginal distribution to tissues compared to total body water following intravenous administration to mouse (Vss 0.57 L/kg), rat (Vss 0.70 L/kg), and dog (Vss 0.25 L/kg).

Cell Research(from reference)

Cell lines：TM3 Wnt-Luc cells and L-cell Wnt3A cells 

Incubation Time：24 h 

Specifications

Synonyms

[2, ​4'-​Bipyridine]​-​5-​acetamide, N-​[5-​(4-​acetyl-​1-​piperazinyl)​-​2-​pyridinyl]​-​2'-​fluoro-​3-​methyl-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

GNF-6231 is a potent, orally active and selective Porcupine inhibitor with IC50 of 0.8 nM.

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.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of porcupine O-acyltransferase

Names and Identifiers

• Canonical Smiles: CC1=CC(=CN=C1C2=CC(=NC=C2)F)CC(=O)NC3=NC=C(C=C3)N4CCN(CC4)C(=O)C
• IUPAC Name: N-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]-2-[6-(2-fluoropyridin-4-yl)-5-methylpyridin-3-yl]acetamide
• InChIKey: AXXNRMISICMFNS-UHFFFAOYSA-N
• INCHI: 1S/C24H25FN6O2/c1-16-11-18(14-28-24(16)19-5-6-26-21(25)13-19)12-23(33)29-22-4-3-20(15-27-22)31-9-7-30(8-10-31)17(2)32/h3-6,11,13-15H,7-10,12H2,1-2H3,(H,27,29,33)
• Isomeric SMILES: CC1=CC(=CN=C1C2=CC(=NC=C2)F)CC(=O)NC3=NC=C(C=C3)N4CCN(CC4)C(=O)C
• Molecular Weight: 448.49
• Reaxy-Rn: 20663882
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=20663882&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Diazinanes
      • Subclass Piperazines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Diazinanes
• Subclass: Piperazines
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridinylpiperazines
• Alternative Parents: Bipyridines and oligopyridines N-arylpiperazines Dialkylarylamines N-arylamides 2-halopyridines Aminopyridines and derivatives Methylpyridines Aryl fluorides Imidolactams Heteroaromatic compounds Tertiary carboxylic acid amides Acetamides Secondary carboxylic acid amides Amino acids and derivatives Azacyclic compounds Organic oxides Carbonyl compounds Organofluorides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Bipyridine - N-arylpiperazine - Pyridinylpiperazine - Dialkylarylamine - N-arylamide - Aminopyridine - 2-halopyridine - Methylpyridine - Aryl fluoride - Aryl halide - Pyridine - Imidolactam - Heteroaromatic compound - Acetamide - Tertiary carboxylic acid amide - Amino acid or derivatives - Carboxamide group - Tertiary amine - Secondary carboxylic acid amide - Carboxylic acid derivative - Azacycle - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organooxygen compound - Organic nitrogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as pyridinylpiperazines. These are compounds containing a pyridinylpiperazine skeleton, which consists of a pyridine linked (not fused) to a piperazine by a bond by a single bond that is not part of a ring.
• 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)

PORCN Tchem Protein-serine O-palmitoleoyltransferase porcupine (0 Activities)

Discover Target: PORCN

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

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

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

Associated Targets(non-human)

Mus musculus (284745 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

• Molecular Weight: 448.500 g/mol
• XLogP3: 1.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 5
• Exact Mass: 448.202 Da
• Monoisotopic Mass: 448.202 Da
• Topological Polar Surface Area: 91.300 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 673.000
• 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