dactolisib   Click here for help

GtoPdb Ligand ID: 7950

Synonyms: BEZ235 | NVP-BEZ235 | RTB-101 | RTB101
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].

COVID-19: Dactolisib (as RTB101) is being evaluated as post-exposure prophylaxis for SARS-CoV-2 infection.
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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
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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
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. Restorbio began investigating dactolisib for potential to treat respiratory tract infections including SARS-CoV-2 infection. However phase 3 study NCT04668352 failed to meet its endpoint and the phase 3 COVID-19 trial NCT04139915 was withdrawn.
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.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04584710 A Phase 2 Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Older Adults Phase 2 Interventional Restorbio Inc.
NCT04668352 A Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly Phase 3 Interventional Restorbio Inc.