volasertib   Click here for help

GtoPdb Ligand ID: 7947

Synonyms: BI 6727 | BI-6727
PDB Ligand
Compound class: Synthetic organic
Comment: Volasertib is an ATP-competitive, investigational inhibitor of polo-like kinase 1 (PLK1). It is the second in a novel class of drugs called dihydropteridinone derivatives [3]. This compound is represented on PubChem by CID 10461508. This CID varies slightly in its chiral specification from our ligand entry. Our structure was drawn from the image submitted to the WHO for the INN (note that the long chemical name provided for the INN registration is not sufficient to resolve absolute stereochemistry as depicted in the accompanying image). Some bioactivity may be linked to the trihydrochloride salt form.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 10
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 106.17
Molecular weight 618.4
XLogP 4.2
No. Lipinski's rules broken 0
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Canonical SMILES CCC1N(C(C)C)c2nc(ncc2N(C1=O)C)Nc1ccc(cc1OC)C(=O)NC1CCC(CC1)N1CCN(CC1)CC1CC1
Isomeric SMILES CC[C@H]1N(C(C)C)c2nc(ncc2N(C1=O)C)Nc1ccc(cc1OC)C(=O)N[C@@H]1CC[C@H](CC1)N1CCN(CC1)CC1CC1
InChI InChI=1S/C34H50N8O3/c1-6-28-33(44)39(4)29-20-35-34(38-31(29)42(28)22(2)3)37-27-14-9-24(19-30(27)45-5)32(43)36-25-10-12-26(13-11-25)41-17-15-40(16-18-41)21-23-7-8-23/h9,14,19-20,22-23,25-26,28H,6-8,10-13,15-18,21H2,1-5H3,(H,36,43)(H,35,37,38)/t25-,26-,28-/m1/s1
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Summary of Clinical Use Click here for help
In 2013, the US FDA granted volasertib breakthrough therapy designation for the treatment of patients with acute myeloid leukemia (AML), in response to positive results from a Phase 2 clinical trial (NCT00804856) in which the drug demonstrated substantial improvement on a clinically significant endpoint (in this case objective response) over available cytarabine therapy. The drug has now progressed to Phase 2I (NCT01721876) in combination with cytarabine for AML patients aged >65 years who have not received prior treatment and who are ineligible for intensive therapy. Phase 2 clinical trials are underway to assess volasertib as a treatment for additional conditions such as ovarian cancer, urothelial cancer and advanced non-small-cell lung cancer.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
PLK1 is ubiquitously present in the nuclei of dividing cells, where it controls several stages of the cell cycle and cell division [1-2]. Inhibition of PLK1 blocks cell division.