Foretinib (GSK1363089) - Moligand™, 10mM in DMSO , Vascular endothelial growth factor receptor inhibitor, CAS No.849217-64-7, Vascular endothelial growth factor receptor inhibitor

CAS: 849217-64-7 Cat. No.: F407825 Molecular Weight: 632.65 EC Number: 629-893-0

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

EXEL-2880, XL-880, GSK089 | N-(3-fluoro-4-(6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Foretinib (GSK1363089, EXEL-2880, XL-880, GSK089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly forMet (c-Met)andKDRwithIC50of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β and Tie-2, and litt
In vitro

XL880 inhibits HGF receptor family tyrosine kinases with IC50 values of 0.4 nM for Met and 3 nM for Ron. XL880 also inhibits KDR, Flt-1, and Flt-4 with IC50 values of 0.9 nM, 6.8 nM and 2.8 nM, respectively. XL880 inhibits colony growth of B16F10, A549 and HT29 cells with IC50 of 40 nM, 29 nM and 165 nM, respectively. A recent study indicates XL880 affects cell growth differently in gastric cancer cell lines MKN-45 and KATO-III. XL880 inhibits phosphorylation of MET and downstream signaling molecules in MKN-45 cells, while targets GFGR2 in KATO-III cells.

In vivo

A single 100 mg/kg oral gavage dose of XL880 results in substantial inhibition of phosphorylation of B16F10 tumor Met and ligand (e.g., HGFor VEGF)-induced receptor phosphorylation of Met in liver and Flk-1/KDR in lung, which both persisted through 24 hours. Treatment with XL880 (30-100 mg/kg, once daily, oral gavage) results in reduction in tumor burden. The lung surface tumor burden is reduced by 50% and 58% following treatment with 30 and 100 mg/kg XL880, respectively. XL880 treatment of mice bearing B16F10 solid tumors also results in dose-dependent tumor growth inhibition of 64% and 87% at 30 and 100 mg/kg, respectively. For both studies, administration of XL880 is well tolerated with no significant body weight loss. XL880 is developed to target abnormal signaling of HGF through Met and simultaneously target several receptors tyrosine kinase involved in tumor angiogenesis. XL880 caused tumor hemorrhage and necrosis in human xenografts within 2 to 4 hours, and maximal tumornecrosis is observed at 96 hours (after five daily doses), resulting in complete regression.
Cell Data

cell lines：Swiss 3T3

Concentrations：40 nM

Incubation Time：12 to 14 days

Powder Purity:≥95%

Specifications

Synonyms

EXEL-2880, XL-880, GSK089 | N-(3-fluoro-4-(6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Foretinib (GSK1363089, EXEL-2880, XL-880, GSK089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met (c-Met) and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β and Tie-2, an

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

Vascular endothelial growth factor receptor inhibitor

Product Properties

• ALogP: 5.5

Names and Identifiers

• Isomeric SMILES: COC1=CC2=C(C=CN=C2C=C1OCCCN3CCOCC3)OC4=C(C=C(C=C4)NC(=O)C5(CC5)C(=O)NC6=CC=C(C=C6)F)F
• Molecular Weight: 632.65
• Reaxy-Rn: 18631787
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=18631787&ln=

Associated Targets(Human)

C8orf76 Tdark Uncharacterized protein C8orf76 (0 Activities)

Discover Target: C8orf76

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

CDK7 Tchem Cyclin-dependent kinase 7 (1 Activities)

Discover Target: CDK7

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

EPHA4 Tchem Ephrin type-A receptor 4 (1 Activities)

Discover Target: EPHA4

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

EPHA8 Tchem Ephrin type-A receptor 8 (1 Activities)

Discover Target: EPHA8

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

EPHB6 Tchem Ephrin type-B receptor 6 (1 Activities)

Discover Target: EPHB6

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

DDR2 Tchem Discoidin domain-containing receptor 2 (1 Activities)

Discover Target: DDR2

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

EPHA1 Tchem Ephrin type-A receptor 1 (1 Activities)

Discover Target: EPHA1

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

CSF1R Tclin Macrophage colony-stimulating factor 1 receptor (1 Activities)

Discover Target: CSF1R

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

DDR1 Tchem Epithelial discoidin domain-containing receptor 1 (2 Activities)

Discover Target: DDR1

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

RET Tclin Proto-oncogene tyrosine-protein kinase receptor Ret (5 Activities)

Discover Target: RET

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

PTK6 Tchem Protein-tyrosine kinase 6 (1 Activities)

Discover Target: PTK6

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

SRC Tclin Proto-oncogene tyrosine-protein kinase Src (2 Activities)

Discover Target: SRC

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

MST1R Tchem Macrophage-stimulating protein receptor (10 Activities)

Discover Target: MST1R

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

ROS1 Tclin Proto-oncogene tyrosine-protein kinase ROS (5 Activities)

Discover Target: ROS1

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

FLT4 Tclin Vascular endothelial growth factor receptor 3 (7 Activities)

Discover Target: FLT4

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

TYRO3 Tchem Tyrosine-protein kinase receptor TYRO3 (1 Activities)

Discover Target: TYRO3

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

EPHA7 Tchem Ephrin type-A receptor 7 (2 Activities)

Discover Target: EPHA7

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

HIPK4 Tchem Homeodomain-interacting protein kinase 4 (1 Activities)

Discover Target: HIPK4

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

FLT3 Tclin Receptor-type tyrosine-protein kinase FLT3 (17 Activities)

Discover Target: FLT3

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

MET Tclin Hepatocyte growth factor receptor (56 Activities)

Discover Target: MET

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)

SMO Tclin Smoothened homolog (2 Activities)

Discover Target: SMO

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

TEK Tclin Angiopoietin-1 receptor (2 Activities)

Discover Target: TEK

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

SLK Tchem STE20-like serine/threonine-protein kinase (1 Activities)

Discover Target: SLK

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

PLK4 Tchem Serine/threonine-protein kinase PLK4 (1 Activities)

Discover Target: PLK4

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

PDGFRA Tclin Platelet-derived growth factor receptor alpha (6 Activities)

Discover Target: PDGFRA

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

PDGFRB Tclin Platelet-derived growth factor receptor beta (5 Activities)

Discover Target: PDGFRB

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

MKNK2 Tchem MAP kinase-interacting serine/threonine-protein kinase 2 (1 Activities)

Discover Target: MKNK2

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

MAP2K2 Tclin Dual specificity mitogen-activated protein kinase kinase 2 (1 Activities)

Discover Target: MAP2K2

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

LCK Tclin Tyrosine-protein kinase Lck (1 Activities)

Discover Target: LCK

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

MAP4K5 Tchem Mitogen-activated protein kinase kinase kinase kinase 5 (1 Activities)

Discover Target: MAP4K5

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

LYN Tclin Tyrosine-protein kinase Lyn (1 Activities)

Discover Target: LYN

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

BCR Tclin Breakpoint cluster region protein (1 Activities)

Discover Target: BCR

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

BLK Tchem Tyrosine-protein kinase Blk (1 Activities)

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

AURKC Tchem Aurora kinase C (1 Activities)

Discover Target: AURKC

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

FLT1 Tclin Vascular endothelial growth factor receptor 1 (6 Activities)

Discover Target: FLT1

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

KDR Tclin Vascular endothelial growth factor receptor 2 (18 Activities)

Discover Target: KDR

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

ABL2 Tchem Tyrosine-protein kinase ABL2 (1 Activities)

Discover Target: ABL2

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

ABL1 Tclin Tyrosine-protein kinase ABL1 (5 Activities)

Discover Target: ABL1

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

AXL Tchem Tyrosine-protein kinase receptor UFO (3 Activities)

Discover Target: AXL

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

TIE1 Tchem Tyrosine-protein kinase receptor Tie-1 (1 Activities)

Discover Target: TIE1

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

KIT Tclin Mast/stem cell growth factor receptor Kit (16 Activities)

Discover Target: KIT

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

NTRK2 Tclin BDNF/NT-3 growth factors receptor (1 Activities)

Discover Target: NTRK2

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

NTRK1 Tclin High affinity nerve growth factor receptor (1 Activities)

Discover Target: NTRK1

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

NTRK3 Tclin NT-3 growth factor receptor (1 Activities)

Discover Target: NTRK3

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

MAP2K1 Tclin Dual specificity mitogen-activated protein kinase kinase 1 (1 Activities)

Discover Target: MAP2K1

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

MAP2K5 Tchem Dual specificity mitogen-activated protein kinase kinase 5 (1 Activities)

Discover Target: MAP2K5

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

MUSK Tchem Muscle, skeletal receptor tyrosine-protein kinase (1 Activities)

Discover Target: MUSK

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

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 50 mg/mL (199.16 mM)

References

1. QIAN HU, MENGYAO WANG, JINJIN WANG, YALI TAO, TING NIU.  (2024)  Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.  ONCOLOGY RESEARCH,      [PMID:38560563] [10.32604/or.2023.043647]