G-749 - Moligand™, ≥98% , Inhibitor of fms related receptor tyrosine kinase 3;Inhibitor of MER proto-oncogene; tyrosine kinase, CAS No.1457983-28-6, Inhibitor of fms related receptor tyrosine kinase 3;Inhibitor of MER proto-oncogene; tyrosine kinase

CAS: 1457983-28-6 Cat. No.: G413776 Molecular Weight: 521.41

GRADE & PURITY Moligand™, ≥98%

Synonyms

38-bromo-11-methyl-6-oxa-2,4-diaza-3(2,4)-pyrido[4,3-d]pyrimidina-1(4)-piperidina-5(1,4),7(1)-dibenzenaheptaphan-35(36H)-one | UNII-B06W426B66 | A899265 | Q7825530 | 1457983-28-6 | Q27077763 | G 749 | MFCD28167815 | 8-Bromo-2-[(1-methyl-4-piperidinyl)amin

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

G-749 G-749 is a novel and potent FLT3 inhibitor with IC50 of 0.4 nM, 0.6 nM and 1 nM for FLT3 (WT), FLT3 (D835Y), and Mer, respectively, showing lower potency against other tyrosine kinases.

Targets

FLT3 (Cell-free assay); FLT3 (D835Y) (Cell-free assay); Mer (Cell-free assay); Aurora B (Cell-free assay); RET (Cell-free assay) 15501,0.4 nM; 0.6 nM; 1 nM; 6 nM; 9 nM

In vitro

In FLT3-WT-bearing RS4-11 cells and FLT3-ITD-harboring MV4-11 and Molm-14 cells, G-749 potently inhibits autophosphorylation of FLT3 with IC50 of ≤8 nM. In leukemia cells, G-749 shows antiproliferative activity by inducing apoptosis. In BaF3 cell lines that stably express FLT3-ITD/N676D, FLT3-ITD/F691L, FLT3-D835Y, or FLT3-D835Y/N676D, G-749 shows strong inhibitory activity with IC50 of <10 nM, and thus overcomes drug resistance. In blasts of AML patients, G-749 also exhibits potent antileukemia activity.

In vivo

In MV4-11 xenograft mice, G-749 (30 mg/kg p.o.) effectively inhibits the FLT3 pathway and significant inhibits tumor growth. In an orthogonal model of bone marrow engraftment using Molm-14 cells, G-749 (20 mg/kg p.o.) also inhibits tumor growth and increases survival.

Cell Research(from reference)

Cell lines：MV4-11, RS4-11, K562, HEL, and Molm-14 cells 

Concentrations：~1 μM 

Incubation Time：72 hours 

Specifications

Synonyms

38-bromo-11-methyl-6-oxa-2, 4-diaza-3(2, 4)-pyrido[4, 3-d]pyrimidina-1(4)-piperidina-5(1, 4), 7(1)-dibenzenaheptaphan-35(36H)-one | UNII-B06W426B66 | A899265 | Q7825530 | 1457983-28-6 | Q27077763 | G 749 | MFCD28167815 | 8-Bromo-2-[(1-methyl-4-piperidinyl)amin

Specifications & Purity

Moligand™, ≥98%

Biochemical and Physiological Mechanisms

G-749 is a novel and potent FLT3 inhibitor with IC50 of 0.4 nM, 0.6 nM and 1 nM for FLT3 (WT), FLT3 (D835Y), and Mer, respectively, showing lower potency against other tyrosine kinases.

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

Inhibitor of fms related receptor tyrosine kinase 3;Inhibitor of MER proto-oncogene; tyrosine kinase

Purity

≥98%

Names and Identifiers

• Pubchem Sid: 504772431
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504772431
• Canonical Smiles: CN1CCC(CC1)NC2=NC3=C(C(=O)NC=C3Br)C(=N2)NC4=CC=C(C=C4)OC5=CC=CC=C5
• IUPAC Name: 8-bromo-2-[(1-methylpiperidin-4-yl)amino]-4-(4-phenoxyanilino)-6H-pyrido[4,3-d]pyrimidin-5-one
• InChIKey: SXWMIXPJPNCXQQ-UHFFFAOYSA-N
• INCHI: 1S/C25H25BrN6O2/c1-32-13-11-17(12-14-32)29-25-30-22-20(26)15-27-24(33)21(22)23(31-25)28-16-7-9-19(10-8-16)34-18-5-3-2-4-6-18/h2-10,15,17H,11-14H2,1H3,(H,27,33)(H2,28,29,30,31)
• Isomeric SMILES: CN1CCC(CC1)NC2=NC3=C(C(=O)NC=C3Br)C(=N2)NC4=CC=C(C=C4)OC5=CC=CC=C5
• Alternate CAS: 1457983-33-3
• Molecular Weight: 521.41
• Reaxy-Rn: 24014667
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=24014667&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Diphenylethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Diphenylethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diphenylethers
• Alternative Parents: Diarylethers Pyridopyrimidines Aniline and substituted anilines Phenoxy compounds Phenol ethers Aminopyrimidines and derivatives Pyridinones Aryl bromides Piperidines Imidolactams Vinylogous amides Heteroaromatic compounds Trialkylamines Lactams Azacyclic compounds Hydrocarbon derivatives Organic oxides Organobromides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Diphenylether - Diaryl ether - Pyridopyrimidine - Phenol ether - Aniline or substituted anilines - Phenoxy compound - Aminopyrimidine - Pyridinone - Pyridine - Piperidine - Imidolactam - Pyrimidine - Aryl bromide - Aryl halide - Heteroaromatic compound - Vinylogous amide - Lactam - Tertiary aliphatic amine - Tertiary amine - Ether - Azacycle - Organoheterocyclic compound - Organobromide - Organohalogen compound - Organic nitrogen compound - Amine - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organonitrogen compound - Organooxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether 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)

FLT3 Tclin Receptor-type tyrosine-protein kinase FLT3 (1 Activities)

Discover Target: FLT3

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

MERTK Tchem Tyrosine-protein kinase Mer (1 Activities)

Discover Target: MERTK

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

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

HepG2 (196354 Activities)

Explore this target

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

MV4-11 (7307 Activities)

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

MOLM-14 (399 Activities)

Explore this target

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

Associated Targets(non-human)

BaF3 (4657 Activities)

Explore this target

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: 24 mg/mL warmed with 50ºC Water: bath (46.02 mM); Water: Insoluble; Ethanol: Insoluble
• Molecular Weight: 521.400 g/mol
• XLogP3: 4.900
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 520.122 Da
• Monoisotopic Mass: 520.122 Da
• Topological Polar Surface Area: 91.400 Ų
• Heavy Atom Count: 34
• Formal Charge: 0
• Complexity: 716.000
• 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