Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C23H24FN9O |
Molecular Weight | 461.4948 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@]1(CCCN1C2=NN3C=CC=C3C(NC4=NNC(=C4)C5CC5)=N2)C(=O)NC6=CN=C(F)C=C6
InChI
InChIKey=LQVXSNNAFNGRAH-QHCPKHFHSA-N
InChI=1S/C23H24FN9O/c1-23(21(34)26-15-7-8-18(24)25-13-15)9-3-10-32(23)22-28-20(17-4-2-11-33(17)31-22)27-19-12-16(29-30-19)14-5-6-14/h2,4,7-8,11-14H,3,5-6,9-10H2,1H3,(H,26,34)(H2,27,28,29,30,31)/t23-/m0/s1
Molecular Formula | C23H24FN9O |
Molecular Weight | 461.4948 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/19996272Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/25748921
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19996272
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/25748921
BMS-754807 is a small-molecule insulin-like growth factor 1 receptor (IGF-1R) antagonist that was being developed by Bristol-Myers Squibb. BMS-754807 is a potent and reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor family kinases (Ki, <2 nmol/L). It is currently in phase II development for the treatment of a variety of human cancers. BMS-754807 effectively inhibits the growth of a broad range of human tumor types in vitro, including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, gastric), and hematopoietic (multiple myeloma and leukemia) tumor cell lines (IC50, 5-365 nmol/L); the compound caused apoptosis in a human rhabdomyosarcoma cell line, Rh41, as shown by an accumulation of the sub-G1 fraction, as well as by an increase in poly ADP ribose polymerase and Caspase 3 cleavage. BMS-754807 is active in vivo in multiple (epithelial, mesenchymal, and hematopoietic) xenograft tumor models with tumor growth inhibition ranging from 53% to 115% and at a minimum effective dose of as low as 6.25 mg/kg dosed orally daily. Combination studies with BMS-754807 have been done on multiple human tumor cell types and showed in vitro synergies (combination index, <1.0) when combined with cytotoxic, hormonal, and targeted agents. The combination of cetuximab and BMS-754807 in vivo, at multiple dose levels, resulted in improved clinical outcome over single agent treatment. These data show that BMS-754807 is an efficacious, orally active growth factor 1 receptor/insulin receptor family-targeted kinase inhibitor that may act in combination with a wide array of established anticancer agents.
Originator
Sources: http://adisinsight.springer.com/drugs/800029975
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1957 |
2.0 nM [IC50] | ||
Target ID: CHEMBL1981 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19996272 |
1.7 nM [IC50] | ||
Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19996272 |
6.0 nM [IC50] | ||
Target ID: CHEMBL2815 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19996272 |
4.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
50 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19996272 |
12.5 mg/kg single, oral dose: 12.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
BMS-754807 serum | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. | 2009 Dec 10 |
|
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. | 2014 Jul 15 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01225172
Tablet, Oral, 100 mg, Daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19996272
BMS-754807 effectively inhibits the growth of a broad range of human tumor types in vitro, including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, gastric), and hematopoietic (multiple myeloma and leukemia) tumor cell lines (IC50, 5-365 nmol/L)
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 17:15:26 GMT 2023
by
admin
on
Fri Dec 15 17:15:26 GMT 2023
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Record UNII |
W9E3353E8J
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Record Status |
Validated (UNII)
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Record Version |
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24785538
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1001350-96-4
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C74043
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DB15399
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CHEMBL575448
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100000175499
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W9E3353E8J
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LABELED -> NON-LABELED |
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