RO4929097   Click here for help

GtoPdb Ligand ID: 7338

Synonyms: Ro4929097
Compound class: Synthetic organic
Comment: RO4929097 as an inhibitor of γ-secretase, was originally developed for Alzheimer's disease but based on its ability to inhibit NOTCH it is now being tested as a therapeutic strategy against melanoma and other tumors [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 87.3
Molecular weight 469.14
XLogP 5.6
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES O=C1Nc2ccccc2c2c(C1NC(=O)C(C(=O)NCC(C(F)(F)F)(F)F)(C)C)cccc2
Isomeric SMILES O=C1Nc2ccccc2c2c([C@@H]1NC(=O)C(C(=O)NCC(C(F)(F)F)(F)F)(C)C)cccc2
InChI 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
InChI Key OJPLJFIFUQPSJR-INIZCTEOSA-N
References
1. Huynh C, Poliseno L, Segura MF, Medicherla R, Haimovic A, Menendez S, Shang S, Pavlick A, Shao Y, Darvishian F et al.. (2011)
The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma.
PLoS ONE, 6 (9): e25264. [PMID:21980408]
2. Luistro L, He W, Smith M, Packman K, Vilenchik M, Carvajal D, Roberts J, Cai J, Berkofsky-Fessler W, Hilton H et al.. (2009)
Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties.
Cancer Res., 69 (19): 7672-80. [PMID:19773430]
3. Strosberg JR, Yeatman T, Weber J, Coppola D, Schell MJ, Han G, Almhanna K, Kim R, Valone T, Jump H et al.. (2012)
A phase II study of RO4929097 in metastatic colorectal cancer.
Eur. J. Cancer, 48 (7): 997-1003. [PMID:22445247]
4. Tolcher AW, Messersmith WA, Mikulski SM, Papadopoulos KP, Kwak EL, Gibbon DG, Patnaik A, Falchook GS, Dasari A, Shapiro GI et al.. (2012)
Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors.
J. Clin. Oncol., 30 (19): 2348-53. [PMID:22529266]