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].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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
No information available.
Summary of Clinical Use Click here for help
Dactolisib (as BEZ235) progressed to clinical evaluation in a number of solid tumour types, the most advanced of which were Phase 2 trials. Click here to link to ClinicalTrials.gov's full list of dactolisib trials.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Dactolisib specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway [2]. This action may trigger the translocation of cytosolic Bax (a proapoptotic Bcl2 family member) to the mitochondrial outer membrane, increasing mitochondrial membrane permeability, the result of which is apoptotic cell death.