- Guide to PHARMACOLOGY
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  and in addition, it effectively targets ATR with IC50 of 21 nM in cells .
COVID-19: Dactolisib (as RTB101) is being evaluated as post-exposure prophylaxis for SARS-CoV-2 infection.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|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 However phase 3 study NCT04668352 failed to meet its endpoint and the phase 3 COVID-19 trial NCT04139915 was withdrawn.|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|
|Dactolisib specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway . 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 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.|