BMS-777607 化学構造
分子量: 512.89





  • Compare c-Met Inhibitors
  • 研究分野
  • BMS-777607のメカニズム



製品説明 BMS777607は分子が小さいMet関連キナーゼ阻害剤、c-Met, Axl, Ron 、Tyro3に作用する時、IC50がそれぞれ3.9nM、1.1nM、1.8nMと4.3nMになる。
ターゲット c-Met Axl Ron Tyro3
IC50 3.9 nM 1.1 nM 1.8 nM 4.3 nM [1]
In vitro試験 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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
GTL-16 MnfGT4lv[XOnIHHzd4F6 M{SyZ2ROW09? M2\1fIlvcGmkaYTzJG1mfCCtaX7hd4Uhf2m2aDDJR|UxKG:oIEGwNEBvVQ>? NH;Z[4EyQTJ4MEexNS=>
H1993 M2DjNGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M37YOJ4yOCEQvF2= M4rremROW09? NFq0T2xKSzVyPUG1NEBvVQ>? M4f0VVE6OjZyN{Gx
U87 M3G1fGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NWHGVGpQhjFyIN88US=> MmTYSG1UVw>? NXL2Tox7UUN3ME2xOlAhdk1? NYSwS3NKOTl{NkC3NVE>
PC-3 NWfwUo1mTnWwY4Tpc44h[XO|YYm= MYOwMlEh|ryP MorMSG1UVw>? NIXDU3ZmgGirYnn0d{BqdmirYnn0c5J6KGWoZnXjeEBwdiCKR1[tbY5lfWOnZDDj[YxtKHOlYYT0[ZJqdmd? NXuyS4VLOjB3MUW5OFM>
DU145 MV3GeY5kfGmxbjDhd5NigQ>? M3rvTFAvOSEQvF2= MWrEUXNQ MVXlfIhq[mm2czDpcohq[mm2b4L5JIVn\mWldDDvckBJT0ZvaX7keYNm\CClZXzsJJNk[XS2ZYLpcoc> NITvNFMzODVzNUm0Ny=>
PC-3 NUj0SphGTnWwY4Tpc44h[XO|YYm= MVywMlAyKM7:TR?= MnnOSG1UVw>? NXPlXWpie3WycILld5NmeyCKR1[tbY5lfWOnZDDj[YxtKG2rZ4LheIlwdg>? NH\ZSGczODVzNUm0Ny=>
DU145 NVj6T29nTnWwY4Tpc44h[XO|YYm= MlX3NE4xOSEQvF2= MWjEUXNQ NYDjdmZje3WycILld5NmeyCKR1[tbY5lfWOnZDDj[YxtKG2rZ4LheIlwdg>? MYCyNFUyPTl2Mx?=
DU145 NU\Wc456TnWwY4Tpc44h[XO|YYm= MY[wMlEh|ryP NILzcWhFVVOR MXvpcZBicXK|IFjHSk1u\WSrYYTl[EBk\WyuIHnueoF{cW:w NWDLNGNxOjB3MUW5OFM>
PC-3 MlSwS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MYf+NVAh|ryP Mn6wSG1UVw>? Mon2doVlfWOnczDj[YxtKHC{b3zp[oVz[XSrb36= Mm\1NlA2OTV7NEO=
KHT MUjLbY5ie2ViYYPzZZk> MULEUXNQ M1XobYJtd2OtczD0bIUh[y2PZYSgd4lodmGuaX7nJJBifGi5YYmge4l1cCCLQ{WwJI9nKDFyIH7N M3L1SlIzOjh4NUKz
KHT M1HPdGZ2dmO2aX;uJIF{e2G7 NGHHPWN,OSEQvF2= MUTEUXNQ MmTNdJJmfmWwdIOgd5BwdnSjbnXveZMhU0iWIHPlcIwhe2OjdITldolv\yC5aYToJGlEPTBib3[gNE4yNTBwNTFOwG0> NG\lc3EzOjJ6NkWyNy=>
KHT NWrSVWwxTnWwY4Tpc44h[XO|YYm= NUiwTWZZhjBwNTFOwG0> M33DSmROW09? NXLmRlYxcW6qaXLpeJMh[2WubDDtbYdz[XSrb36= Mn3aNlIzQDZ3MkO=
KHT NHq2WJFHfW6ldHnvckBie3OjeR?= Mnq5glAvPSEQvF2= NUT0OoptTE2VTx?= Mn\mbY5pcWKrdIOgZ4VtdCCrbo\hd4lwdg>? Mo\WNlIzQDZ3MkO=
KHT NEOxbIVIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MYf+NVAh|ryP MlXSSG1UVw>? NELqdFhqdmirYnn0d{BMUFRiY3XscEBxem:uaX\ldoF1cW:w MY[yNlI5PjV{Mx?=
T-47D NWrwNlNZT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M2f3RZ42KM7:TR?= MkHaSG1UVw>? MoPxbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;u NG\EVHIzOzR4OEWyPS=>
ZR-75-1 M4nlVmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M1nrVJ42KM7:TR?= MV;EUXNQ NUjvfHpDcW6qaXLpeJMh[2WubDDwdo9tcW[ncnH0bY9v NF\2N4QzOzR4OEWyPS=>
T-47D MnXQSpVv[3Srb36gZZN{[Xl? NHflTVkyOCEQvF2= Mn7TSG1UVw>? MkfFTY5lfWOnczDwc4x6eGyxaXT5JIJ6KDh4IDW= MoflNlM1Pjh3Mkm=
ZR-75-1 MmnmSpVv[3Srb36gZZN{[Xl? MWKxNEDPxE1? NYDkSXRGTE2VTx?= NWPn[4xDUW6mdXPld{Bxd2y7cHzvbYR6KGK7IEi4KS=> M4PyVFI{PDZ6NUK5
T-47D MYDGeY5kfGmxbjDhd5NigQ>? M2HqN|ExKM7:TR?= MofUSG1UVw>? M1nJUYlvcGmkaYTzJGFWWktvQjDmeY5kfGmxbjDhcoQhcW6mdXPld{BqfHNicILveIVqdiCmZXfyZYRifGmxbh?= M2OzTFI{PDZ6NUK5
CHRF NGjpUGpHfW6ldHnvckBie3OjeR?= NHHlWlkyOCEQvF2= M3fB[mROW09? MV7pcohq[mm2czDj[YxtKGSrdnnzbY9v M3zZd|I2OzB2OUCw
HPDE MYnGeY5kfGmxbjDhd5NigQ>? NHrxPVYyOCEQvF2= MY\EUXNQ MYjicI9kc3NiY3;ud5RqfHW2aY\lJIFkfGm4YYTpc44h[W6mIHTlZ5Jm[XOnZDDBT3Qhe2mpbnHsbY5o NIrWXVYzPjR5N{OxOC=>
U118MG MWPLbY5ie2ViYYPzZZk> M{nVdJ4{KM7:TR?= NUPKTIt7TE2VTx?= NFnIZWxjdG:la4OgRXhNKHCqb4PwbI9zgWyjdHnvci=> NWf5dmtQOjZ6NEi1NlQ>
SF126 NF;YUpdMcW6jc3WgZZN{[Xl? MYH+N{DPxE1? MYTEUXNQ NXToV4s3[myxY3vzJGFZVCCyaH;zdIhwenmuYYTpc44> MnGxNlY5PDh3MkS=
U118MG NV7OeJN2S3m2b4jpZ4l1gSCjc4PhfS=> MV6xNk42KM7:TR?= Mn:ySG1UVw>? NGfIV|dl\WO{ZXHz[ZMh\2yrb33hJINmdGxidnnhZoltcXS7 NUX6OGF5OjZ6NEi1NlQ>
SF126 NGnSToZEgXSxeHnjbZR6KGG|c3H5 NY\WV3l{OTJwNTFOwG0> NV3K[|Z5TE2VTx?= NXmyb|ZW\GWlcnXhd4V{KGeuaX;tZUBk\WyuII\pZYJqdGm2eR?= MWqyOlg1QDV{NB?=
SF126 MWHBdI9xfG:|aYOgZZN{[Xl? NHvJdYsyOi53IN88US=> MUXEUXNQ M1j2[4lv\HWlZYOg[4xqd22jIHPlcIwh[XCxcITvd4l{ MWGyOlg1QDV{NB?=
U118MG MWTGeY5kfGmxbjDhd5NigQ>? MojKNVIvPSEQvF2= M1L0PWROW09? NW\hWXp7[myxY3vzJIdtcW:vYTDj[YxtKG2rZ4LheIlwdiCjbnSgbY53[XOrdnWg[5Jwf3SqIIDheJRmem5? MmLaNlY5PDh3MkS=
SF126 Mk\jSpVv[3Srb36gZZN{[Xl? M37hWlEzNjVizszN MWjEUXNQ Mo\FZoxw[2u|IHfsbY9u[SClZXzsJI1q\3KjdHnvckBidmRiaX72ZZNqfmViZ4Lve5RpKHCjdITldo4> MYWyOlg1QDV{NB?=

... Click to View More Cell Line Experimental Data

In vivo試験 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]
臨床試験 Phase I/II has been completed in the study to find the maximum tolerated dose and the preliminary activity of BMS-777607 in subjects with advanced or metastatic solid tumors, hormone refractory prostate cancer, head and neck squamous cell carcinoma, and t
特集 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.

プロトコル (参考用のみ)

キナーゼアッセイ: [4]

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 dimethylsulfoxide (DMSO) and evaluated at 10 concentrations, in duplicate.

細胞アッセイ: [3]

細胞株 Rodent fibrosarcoma KHT cells
濃度 Dissolved in DMSO as a stock solution (10 mM), final concentration ~10 μM.
反応時間 2, 24 and 96 hours
実験の流れ 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.

動物実験: [3]

動物モデル Rodent fibrosarcoma KHT cells are established in female C3H/HeJ mice.
製剤 Dissolved in DMSO as a stock solution (10 mM).
投薬量 10-25 mg/kg.
投与方法 Oral gavage once daily.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)



Download BMS-777607 SDF
分子量 512.89


CAS No. 1025720-94-8
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 47 mg/mL (91.63 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 4% DMSO+30% PEG 300+ddH2O 5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID