volasertib   

GtoPdb Ligand ID: 7947

Synonyms: BI 6727 | BI-6727
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.
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
InChI Key SXNJFOWDRLKDSF-STROYTFGSA-N
References
1. Barr FA, Silljé HH, Nigg EA. (2004)
Polo-like kinases and the orchestration of cell division.
Nat. Rev. Mol. Cell Biol., 5 (6): 429-40. [PMID:15173822]
2. Santamaria A, Neef R, Eberspächer U, Eis K, Husemann M, Mumberg D, Prechtl S, Schulze V, Siemeister G, Wortmann L et al.. (2007)
Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis.
Mol. Biol. Cell, 18 (10): 4024-36. [PMID:17671160]
3. Schöffski P. (2009)
Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology.
Oncologist, 14 (6): 559-70. [PMID:19474163]
4. Zhang Q, Xia Z, Mitten MJ, Lasko LM, Klinghofer V, Bouska J, Johnson EF, Penning TD, Luo Y, Giranda VL et al.. (2012)
Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors.
Bioorg. Med. Chem. Lett., 22 (24): 7615-22. [PMID:23103095]