| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H20F5N3O3 |
| Molecular Weight | 469.4045 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(C(=O)NCC(F)(F)C(F)(F)F)C(=O)N[C@H]1C2=C(C=CC=C2)C3=C(NC1=O)C=CC=C3
InChI
InChIKey=OJPLJFIFUQPSJR-INIZCTEOSA-N
InChI=1S/C22H20F5N3O3/c1-20(2,18(32)28-11-21(23,24)22(25,26)27)19(33)30-16-14-9-4-3-7-12(14)13-8-5-6-10-15(13)29-17(16)31/h3-10,16H,11H2,1-2H3,(H,28,32)(H,29,31)(H,30,33)/t16-/m0/s1
RO4929097 (R-4733) is a small-molecule inhibitor of gamma-secretase (γ-secretase) with high oral bioavailability leading to the blockade of Notch signaling in tumor cells. This compound was co-developed by Roche and National Cancer Institute (NCI). RO4929097 had been in phase II clinical trials for the treatment of melanoma, colorectal cancer, and pancreatic cancer. However, these researches has been discontinued. Combination of RO4929097 and bevacizumab was well tolerated in phase I of clinical trial and can be considered in patients with recurrent malignant glioma.
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
RO4929097 at a dose of 20 mg daily 3 consecutive days per week.
Route of Administration:
Oral
RO4929097 decreases the amount of Aβ peptides secreted into the culture medium in HEK293 cells with EC50 of 14 nM also strongly inhibits Notch processing with EC50 of 5 nM in the Notch cell-based reporter assay. The primary in vitro assay used human cell-free membrane preparations to provide the γ-secretase enzyme complex. RO4929097 strongly inhibited γ-secretase enzyme activity with a 4 nM potency. After 5 days of treatment, RO4929097 reduces the production of intracellular Notch (ICN) in the human NSCLC A549 cells inducing a flattened and less transformed tumor cell phenotype in tissue culture.
ACTIVE MOIETY
