adavosertib   Click here for help

GtoPdb Ligand ID: 7702

Synonyms: AZD 1775 | AZD-1775 | AZD1775 | MK-1775 | MK1775
PDB Ligand
Compound class: Synthetic organic
Comment: Adavosertib (AZD1775) inhibits WEE1 G2 checkpoint kinase. It was developed as a potential adjunctive therapeutic for advanced solid tumours. This compound is included in AstaZeneca's Open Innovation Pharmacology Toolbox.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

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

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.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 103.82
Molecular weight 500.26
XLogP 2.79
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES C=CCn1c(=O)c2c(n1c1cccc(n1)C(O)(C)C)nc(nc2)Nc1ccc(cc1)N1CCN(CC1)C
Isomeric SMILES C=CCn1c(=O)c2c(n1c1cccc(n1)C(O)(C)C)nc(nc2)Nc1ccc(cc1)N1CCN(CC1)C
InChI InChI=1S/C27H32N8O2/c1-5-13-34-25(36)21-18-28-26(29-19-9-11-20(12-10-19)33-16-14-32(4)15-17-33)31-24(21)35(34)23-8-6-7-22(30-23)27(2,3)37/h5-12,18,37H,1,13-17H2,2-4H3,(H,28,29,31)
InChI Key BKWJAKQVGHWELA-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Several Phase 2 clinical trials of AZD1775 are underway for a variety of oncological indications including, ovarian, peritoneal or fallopian tube cancers, previously treated non-small-cell lung cancer, childhood refractory solid tumours and recurrent or metastatic head and neck cancer. All of these trials are testing AZD1775 in combination with other chemotherapeutic agents. Click here to link to ClinicalTrials.gov's full listing of AZD1775 Phase 2 trials. Phase 1 clinical trial NCT02617277 has begun, to evaluate combination of AZD1775 with the immune checkpoint inhibitor durvalumab (anti-PD-L1 mAb) in patients with selected advanced solid tumours.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
In vitro, AZD1775 inhibits Wee1 activity, inducing DNA damage and effecting G2 checkpoint escape.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02617277 Safety, Tolerability and Pharmacokinetics of AZD1775 (Adavosertib) Plus MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumours Phase 1 Interventional AstraZeneca