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.
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2D Structure
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Physico-chemical Properties
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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
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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)
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'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