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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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.

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View interactive charts of activity data across species

dactolisib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.