Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C25H19ClF2N4O4 |
| Molecular Weight | 512.893 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCOC1=C(C(=O)NC2=CC=C(OC3=C(Cl)C(N)=NC=C3)C(F)=C2)C(=O)N(C=C1)C4=CC=C(F)C=C4
InChI
InChIKey=VNBRGSXVFBYQNN-UHFFFAOYSA-N
InChI=1S/C25H19ClF2N4O4/c1-2-35-19-10-12-32(16-6-3-14(27)4-7-16)25(34)21(19)24(33)31-15-5-8-18(17(28)13-15)36-20-9-11-30-23(29)22(20)26/h3-13H,2H2,1H3,(H2,29,30)(H,31,33)
| Molecular Formula | C25H19ClF2N4O4 |
| Molecular Weight | 512.893 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/25304900Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20515943 | https://www.ncbi.nlm.nih.gov/pubmed/26848524 | https://www.ncbi.nlm.nih.gov/pubmed/19260711
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25304900
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20515943 | https://www.ncbi.nlm.nih.gov/pubmed/26848524 | https://www.ncbi.nlm.nih.gov/pubmed/19260711
BMS 777607 is a substituted 2-aminopyridine shown to inhibit the RON and cMet receptor tyrosine kinases, for the treatment of solid tumors. BMS 777607 demonstrated ligand stimulated and constitutive Met phosphorylation, and inhibition of tumor cell proliferation, in preclinical studies. Preclinical data indicated that BMS 777607 inhibited RON, blocking the conversion of micrometastases to overt metastases by boosting antitumor immunity. Bristol-Myers Squibb conducted a phase I/II trial of BMS 777607 for the treatment of advanced solid tumors in Australia. As at December 2016, no recent reports of development had been identified for preclinical development in Cancer in the USA.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
3.9 nM [IC50] | ||
Target ID: CHEMBL2689 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
1.8 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
17.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 plasma | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
29 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 blood | Canis lupus population: UNKNOWN age: ADULT sex: MALE food status: FASTED |
|
8.7 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 blood | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
17.6 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 blood | Mus musculus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
90 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 plasma | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
198 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 blood | Canis lupus population: UNKNOWN age: ADULT sex: MALE food status: FASTED |
|
37.7 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 blood | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
90 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19260711 |
10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-777607 blood | Mus musculus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19260711 |
5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
BMS-777607 plasma | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| BMS-777607, a small-molecule met kinase inhibitor, suppresses hepatocyte growth factor-stimulated prostate cancer metastatic phenotype in vitro. | 2010-06 |
|
| Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. | 2009-03-12 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26848524
U118MG and SF126 cells were implanted stereotactically into the brains of CD1NuNu mice. In the more aggressive tumor SF126 model, treatment was started at day 3 after implantation while treatment in the U118MG model was started on day 7 after implantation. In both models, BMS-777607 treatment (30 or 100 mg/kg, i.p. 2x/day) resulted in a significant decrease of intracranial tumor growth on day 14 after implantation.
Route of Administration:
Intraperitoneal
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26848524
Human high-grade glioma cells U118MG and SF126 glioma cells were treated with BMS-777607 at different concentrations (1.56 mkM–50 mkM). Culture medium was replaced or exchanged after 24, 48 and 72 hours. The exposure of U118MG and SF126 glioma cells with 12.5 μM BMS-777607 resulted in significantly reduced cell numbers in MTT assay after 24 hours of treatment.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 21:23:03 GMT 2025
by
admin
on
Mon Mar 31 21:23:03 GMT 2025
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| Record UNII |
A3MMS6HDO1
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| Record Status |
Validated (UNII)
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| Record Version |
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A3MMS6HDO1
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DB12064
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DTXSID50145278
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C74060
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CHEMBL460702
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24794418
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| Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |