dactolisib   Click here for help

GtoPdb Ligand ID: 7950

Synonyms: BEZ235 | NVP-BEZ235
Compound class: Synthetic organic
Comment: Dactolisib is an orally bioavailable dual PI3K/mTOR inhibitor with potential antineoplastic activity. It inhibits all of the PI3K isoforms [3] and in addition, it effectively targets ATR with IC50 of 21 nM in cells [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 0
Rotatable bonds 3
Topological polar surface area 75.98
Molecular weight 469.19
XLogP 4.92
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#CC(c1ccc(cc1)n1c(=O)n(c2c1c1cc(ccc1nc2)c1cnc2c(c1)cccc2)C)(C)C
Isomeric SMILES N#CC(c1ccc(cc1)n1c(=O)n(c2c1c1cc(ccc1nc2)c1cnc2c(c1)cccc2)C)(C)C
InChI InChI=1S/C30H23N5O/c1-30(2,18-31)22-9-11-23(12-10-22)35-28-24-15-19(21-14-20-6-4-5-7-25(20)32-16-21)8-13-26(24)33-17-27(28)34(3)29(35)36/h4-17H,1-3H3
InChI Key JOGKUKXHTYWRGZ-UHFFFAOYSA-N
References
1. Fròsina G, Profumo A, Marubbi D, Marcello D, Ravetti JL, Daga A. (2018)
ATR kinase inhibitors NVP-BEZ235 and AZD6738 effectively penetrate the brain after systemic administration.
Radiat Oncol, 13 (1): 76. [PMID:29685176]
2. Ma BB, Lui VW, Hui CW, Lau CP, Wong CH, Hui EP, Ng MH, Cheng SH, Tsao SW, Tsang CM et al.. (2014)
Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.
Cancer Lett, 343 (1): 24-32. [PMID:24041865]
3. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chène P, De Pover A, Schoemaker K et al.. (2008)
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity.
Mol Cancer Ther, 7 (7): 1851-63. [PMID:18606717]
4. Toledo LI, Murga M, Zur R, Soria R, Rodriguez A, Martinez S, Oyarzabal J, Pastor J, Bischoff JR, Fernandez-Capetillo O. (2011)
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations.
Nat Struct Mol Biol, 18 (6): 721-7. [PMID:21552262]
5. Willemsen-Seegers N, Uitdehaag JCM, Prinsen MBW, de Vetter JRF, de Man J, Sawa M, Kawase Y, Buijsman RC, Zaman GJR. (2017)
Compound Selectivity and Target Residence Time of Kinase Inhibitors Studied with Surface Plasmon Resonance.
J Mol Biol, 429 (4): 574-586. [PMID:28043854]