Home Protein Tyrosine Kinase c-Met inhibitor - Axl inhibitor - Tyro3 inhibitor - RON inhibitor BMS-777607 For research use only.

BMS-777607

Synonyms: BMS 817378

BMS-777607 (BMS 817378) is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases.

BMS-777607 Chemical Structure

BMS-777607 Chemical Structure

CAS No. 1025720-94-8

Purity & Quality Control

BMS-777607 Related Products

Signaling Pathway

c-Met Signaling Pathways

c-Met Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PC-3 Function assay 0.1 μM DMSO exhibits inhibitory effect on HGF-induced cell scattering 20515943
DU145 Function assay 0.1 μM DMSO exhibits inhibitory effect on HGF-induced cell scattering 20515943
PC-3 Function assay 0.01 μM DMSO suppresses HGF-induced cell migration 20515943
DU145 Function assay 0.01 μM DMSO suppresses HGF-induced cell migration 20515943
PC-3 Function assay 0.1 μM DMSO impairs HGF-mediated cell invasion 20515943
DU145 Function assay 0.1 μM DMSO impairs HGF-mediated cell invasion 20515943
PC-3 Growth inhibitory assay ~10 μM DMSO reduces cell proliferation 20515943
KHT Kinase assay DMSO blocks the c-Met signaling pathway with IC50 of 10 nM 22286523
KHT Function assay ~1 μM DMSO prevents spontaneous KHT cell scattering with IC50 of 0.1-0.5 μM 22286523
KHT Function assay ~0.5 μM DMSO inhibits cell migration 22286523
KHT Function assay ~0.5 μM DMSO inhibits cell invasion 22286523
KHT Growth inhibitory assay ~10 μM DMSO inhibits KHT cell proliferation 22286523
T-47D Growth inhibitory assay ~5 μM DMSO inhibits cell proliferation 23468529
ZR-75-1 Growth inhibitory assay ~5 μM DMSO inhibits cell proliferation 23468529
T-47D Function assay 10 μM DMSO Induces polyploidy by 86 % 23468529
ZR-75-1 Function assay 10 μM DMSO Induces polyploidy by 88% 23468529
T-47D Function assay 10 μM DMSO inhibits AURK-B function and induces its protein degradation 23468529
CHRF Function assay 10 μM DMSO inhibits cell division 25304900
HPDE Function assay 10 μM DMSO blocks constitutive activation and decreased AKT signaling 26477314
U118MG Kinase assay ~3 μM DMSO blocks AXL phosphorylation 26848524
SF126 Kinase assay ~3 μM DMSO blocks AXL phosphorylation 26848524
U118MG Cytoxicity assay 12.5 μM DMSO decreases glioma cell viability 26848524
SF126 Cytoxicity assay 12.5 μM DMSO decreases glioma cell viability 26848524
U118MG Apoptosis assay 12.5 μM DMSO induces glioma cell apoptosis 26848524
SF126 Apoptosis assay 12.5 μM DMSO induces glioma cell apoptosis 26848524
U118MG Function assay 12.5 μM DMSO blocks glioma cell migration and invasive growth pattern 26848524
SF126 Function assay 12.5 μM DMSO blocks glioma cell migration and invasive growth pattern 26848524
GTL16 Function assay 30 mins Inhibition of Met phosphorylation in human GTL16 cells after 30 mins, IC50 = 0.02 μM. 19260711
GTL16 Antiproliferative assay 72 hrs Antiproliferative activity against Met-dependent human GTL16 cells after 72 hrs by MTS assay, IC50 = 0.1 μM. 19260711
NCI-H1993 Antiproliferative assay 72 hrs Antiproliferative activity against Met-dependent human NCI-H1993 cells after 72 hrs by MTS assay, IC50 = 0.15 μM. 19260711
U87 Antiproliferative assay 72 hrs Antiproliferative activity against Met-driven human U87 cells after 72 hrs by MTS assay, IC50 = 0.16 μM. 19260711
BAF3 Cytotoxicity assay 72 hrs Cytotoxicity against mouse BAF3 cells expressing TPR-Met assessed as growth inhibition after 72 hrs, IC50 = 0.1884 μM. 24792774
DU145 Antiinvasive assay 1 hr Antiinvasive activity in human DU145 cells assessed as inhibition of HGF-induced cell motility preincubated for 1 hr before HGF treatment measured after 24 hrs by cell scattering assay, IC50 = 0.2 μM. 24900830
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as growth inhibition after 72 hrs, IC50 = 0.2858 μM. 24792774
NCI-H1993 Cytotoxicity assay 48 hrs Cytotoxicity against human NCI-H1993 cells after 48 hrs by MTT assay, IC50 = 1.108 μM. 24900830
GTL16 Function assay 6.25 mg/kg Cmax in human GTL16 cells xenografted athymic mouse at 6.25 mg/kg, po, Cmax = 4.5 μM. 19260711
GTL16 Function assay 50 mg/kg Cmax in human GTL16 cells xenografted athymic mouse at 50 mg/kg, po, Cmax = 43.7 μM. 19260711
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
MGHU3 Antiproliferative assay 72 hrs Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay 30309671
RT112 Antiproliferative assay 72 hrs Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay 30309671
Click to View More Cell Line Experimental Data

Biological Activity

Description BMS-777607 (BMS 817378) is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases.
Features A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.
Targets
Axl [1]
(Cell-free assay)		 RON [1]
(Cell-free assay)		 Met [1]
(Cell-free assay)		 Tyro3 [1]
(Cell-free assay)		 Mer [1]
(Cell-free assay)		 Click to View More Targets
1.1 nM 1.8 nM 3.9 nM 4.3 nM 14 nM
In vitro
In vitro

BMS-777607 is a selective ATP-competitive Met kinase inhibitor which potently blocks the autophosphorylation of c-Met with IC50 of 20 nM in GTL-16 cell lysates, and demonstrates selective inhibition of proliferation in Met-driven tumor cell lines, such as GTL-16 cell line, H1993 and U87. [1] BMS-777607 inhibits hepatocyte growth factor (HGF)-triggered c-Met autophosphorylation with IC50 of <1 nM in PC-3 and DU145 prostate cancer cells. BMS 777607 has little effect on tumor cell growth, but exhibits inhibitory effect on HGF-induced cell scattering in PC-3 and DU145 cells, with almost complete inhibition at 0.5 μM. BMS 777607 also suppresses stimulated cell migration and invasion in a dose-dependent fashion (IC50 < 0.1 μM) in both cell lines. [2] Application of BMS 777607 (~10 μM) to the highly metastatic murine KHT cells for 2 hours potently eliminates basal levels of autophosphorylated c-Met with IC50 of 10 nM without affecting the total c-Met, leading to dose-dependent inhibition of phosphorylation of downstream signaling molecules including ERK, Akt, p70S6K and S6. Treatment with BMS-777607 (~1 μM) for 24 hours potently inhibits the KHT cell scatter, motility and invasion at doses in the nanomolar range which consists with MET gene knockdown, and modestly affects cell proliferation and colony formation. [3]
Kinase Assay Met Kinase Assay
The kinase reaction consists of baculovirus expressed GST-Met, 3 μg of poly(Glu/Tyr), 0.12 μCi 33P γ-ATP, 1 μM ATP in 30 μL of kinase buffer (20 mM Tris-Cl, 5 mM MnCl2, 0.1 mg/mL BSA, 0.5 mM DTT). Reactions are incubated for 1 hour at 30 °C and stopped by the addition of cold trichloroacetic acid (TCA) to a final concentration of 8%. TCA precipitates are collected onto GF/C unifilter plates using a Filtermate universal harvester, and the filters are quantitated using a TopCount 96-well liquid scintillation counter. Dose response curves are generated to determine the concentration required to inhibit 50% of substrate phosphorylation (IC50). BMS 777607 is dissolved at 10 mM in DMSO and evaluated at 10 concentrations, in duplicate.
Cell Research Cell lines Rodent fibrosarcoma KHT cells
Concentrations Dissolved in DMSO as a stock solution (10 mM), final concentration ~10 μM.
Incubation Time 2, 24 and 96 hours
Method

KHT cells are exposed to serial dilution of BMS 777607 for 96 hours, then the MTT assay and trypan blue exclusion are used for the determination of cell proliferation and cell death, respectively. KHT cell colonies are incubated with BMS 777607 for 24 hours and then stained with crystal violet (0.1%) and photographed for the assessment of cell scattering. 2 mm scratch on the confluent KHT cell monolayer is made using a sterilized 1 ml pipette tip followed by treated with BMS-777607 for 24 hours, then the number of cells that have migrated into the denuded area is counted on 4 random fields for the evaluation of cell migration. For the examination of cell invasion, the commercial transwell inserts (8 μm pore membrane) pre-loaded with Matrigel are incubated with serum-free medium in the presence or absence of BMS 777607 at 37 °C for 2 hours to allow rehydration of Matrigel. Then cells suspended in serum-free medium are loaded onto the top chamber (5 × 103/insert) and complete medium (containing 10% FBS) is used in the lower chamber as a chemoattractant. After incubation for 24 hours, the Matrigel is removed and the inserts are stained with crystal violet. Invaded cells on the underside of the filter are photographed and counted.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-c-Met / c-Met / p-FAK / p-c-Src / p-Akt / p-S6K / p-S6 p53 / p21 / Survivin / p-Rb / Rb 22639908
Immunofluorescence α-tubulin / survivin 24444656
In Vivo
In vivo

Oral administration of BMS 777607 (6.25-50 mg/kg) significantly reduces tumor volumes of the GTL-16 human tumor xenografts in athymic mice with no observed toxicity. [1] Administration of BMS 777607 (25 mg/kg/day) decreases the number of KHT lung tumor nodules (28.3%), improves the morphological hemorrhage, and significantly impairs the metastatic phenotype in the 6-8 week-old female C3H/HeJ mice injected with rodent fibrosarcoma KHT cells without apparent systemic toxicity compared to the control treatment. A low dose of BMS 777607 (10 mg/kg) also offers a mild but not significant inhibition of lung nodule formation compared to the vehicle control. [3]
Animal Research Animal Models Rodent fibrosarcoma KHT cells are established in female C3H/HeJ mice.
Dosages 10-25 mg/kg.
Administration Oral gavage once daily.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01721148 Completed
Malignant Solid Tumour
ASLAN Pharmaceuticals
 October 2012 Phase 1
NCT00605618 Completed
Advanced Solid Tumors
Bristol-Myers Squibb
 March 2008 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 512.89 Formula

C25H19ClF2N4O4
CAS No. 1025720-94-8 SDF Download BMS-777607 SDF
Smiles CCOC1=C(C(=O)N(C=C1)C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C(=NC=C4)N)Cl)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (194.97 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
What formulation can we use to dissolve S1561 for mice in vivo study?

Answer:
S1561 BMS-777607 in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30 mg/ml is a suspension. It is fine for oral gavage. If you are going to use it for injection, please try the following vehicle: 4% DMSO+30% PEG 300+ddH2O. BMS-777607 can be dissolved in it at 5 mg/ml as a clear solution.

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