vistusertib   Click here for help

GtoPdb Ligand ID: 7699

Synonyms: AZD 2014 | AZD-2014 | AZD2014 | cc-551
Compound class: Synthetic organic
Comment: Vistusertib (AZD2014) is a selective inhibitor of Mammalian target of rapamycin (mTOR) serine/ threonine kinase. This compound is included in AstaZeneca's Open Innovation Pharmacology Toolbox.
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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
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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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 CDK toolkit. 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 9
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 92.71
Molecular weight 462.24
XLogP 3.71
No. Lipinski's rules broken 0
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.

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Canonical SMILES CNC(=O)c1cccc(c1)c1ccc2c(n1)nc(nc2N1CCOCC1C)N1CCOCC1C
Isomeric SMILES CNC(=O)c1cccc(c1)c1ccc2c(n1)nc(nc2N1CCOC[C@@H]1C)N1CCOC[C@@H]1C
InChI InChI=1S/C25H30N6O3/c1-16-14-33-11-9-30(16)23-20-7-8-21(18-5-4-6-19(13-18)24(32)26-3)27-22(20)28-25(29-23)31-10-12-34-15-17(31)2/h4-8,13,16-17H,9-12,14-15H2,1-3H3,(H,26,32)/t16-,17-/m0/s1
InChI Key JUSFANSTBFGBAF-IRXDYDNUSA-N
No information available.
Summary of Clinical Use Click here for help
Vistusertib (AZD2014) is being evaluated in more than 10 Phase 2 clinical trials, for various cancers. Indications include advanced/metastatic breast cancers, glioblastoma multiforme, metastatic clear cell renal carcinoma, (metastatic) squamous non-small cell lung cancer, advanced ovarian cancer and advanced gastric adenocarcinoma. Current investigations favour a combination based approach, for example vistusertib and durvalumab in bladder cancer (Phase 1 NCT02546661) and vistusertib plus rituximab in relapsed/refractory diffuse large B cell lymphoma (Phase 2 NCT02752204). Having shown promise in preclinical animal models of ovarian cancer [8] a combination of vistusertib plus paclitaxel was advanced to human trial in patients with high grade serous ovarian and squamous non-small cell lung cancers. Phase 1 results from this trial (NCT02193633) were published by Basu et al. (2018) [1]. In both cancer types the dual therapy regimen achieved a median progression-free survival of 5.8 months (note: the daily vistusertib dose had to be reduced by half, to 25mg, to manage toxicities in the lung cancer patients).
Click here to link to ClinicalTrials.gov's full list of AZD2014 trials.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Vistusertib's anti-cancer effect is achieved by inhibition of mTOR complexes, and at least in part, by resultant inhibition of downstream ribosomal protein S6 kinase B1 (p70S6K) which is a kinase that is involved in promoting protein synthesis, cell growth, and cell proliferation, and which is associated with human cancers.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02193633 A Phase I Trial of the Combination of AZD2014 and Weekly Paclitaxel. Phase 1 Interventional Royal Marsden NHS Foundation Trust
NCT02546661 Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer Phase 1 Interventional AstraZeneca
NCT02752204 An Evaluation AZD2014 Alone and in Combination With Rituximab in Relapsed/Refractory Diffuse Large B Cell Lymphoma Phase 2 Interventional University of Birmingham