| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H27FN8O3 |
| Molecular Weight | 530.5535 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=C2N(C=C1NC(=O)OC[C@@H]3COCCN3)N=CN=C2NC4=CC5=C(C=C4)N(CC6=CC=CC(F)=C6)N=C5
InChI
InChIKey=LUJZZYWHBDHDQX-QFIPXVFZSA-N
InChI=1S/C27H27FN8O3/c1-17-23(34-27(37)39-15-22-14-38-8-7-29-22)13-36-25(17)26(30-16-32-36)33-21-5-6-24-19(10-21)11-31-35(24)12-18-3-2-4-20(28)9-18/h2-6,9-11,13,16,22,29H,7-8,12,14-15H2,1H3,(H,34,37)(H,30,32,33)/t22-/m0/s1
| Molecular Formula | C27H27FN8O3 |
| Molecular Weight | 530.5535 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
BMS 599626 is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM. BMS-599626 is identified as an ATP-competitive inhibitor for HER1 and as an ATP-noncompetitive inhibitor for HER2. BMS-599626 inhibits the proliferation of tumor cells expressing high levels of HER1 and/or HER2, including Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, and PC9 cells. In a phase I trial of solid tumour patients receiving BMS 599626 no doselimiting toxicities were observed during the first cycle. Grade 1 or 2 drugrelated effects were reported and included diarrhoea, nausea, vomiting, rash, fatigue, musculoskeletal pain/cramp and cough. BristolMyers Squibb discontinued development of BMS 599626 for cancer in July 2015
Originator
Approval Year
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Tox targets
PubMed
Patents
Sample Use Guides
Antitumor activity of BMS-599626 was evaluated in mouse xenograft models. For oral administration to mice, BMS-599626 was dissolved in a mixture of propylene glycol/water (50:50). BMS-599626 was administered once-daily to female nude mice with Sal2 mouse salivary gland tumors at doses of 60 mg/kg, 120 mg/kg and 240 mg/kg for 14 days. In separate experiment BMS-599626 was administered once-daily to female nude mice bearing KPL-4 human breast tumors at doses of of 60 mg/kg and 120 mg/kg for 21 days.
Route of Administration:
Oral
BMS-599626 (in submicromolar concentrations) inhibits the proliferation of tumor cells expressing high levels of HER1 and/or HER2, including Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, and PC9 cells. In proliferation assay. Following the addition of BMS-599626 (diluted in culture medium), the cells were cultured for 72 hours and cell viability was determined by measuring the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye.
