PUBLICATION
The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features
- Authors
- Hammarström, L.G., Harmel, R.K., Granath, M., Ringom, R., Gravenfors, Y., Färnegårdh, K., Svensson, P.H., Wennman, D., Lundin, G., Roddis, Y., Kitambi, S.S., Bernlind, A., Lehmann, F., Ernfors, P.
- ID
- ZDB-PUB-170613-9
- Date
- 2016
- Source
- Journal of medicinal chemistry 59: 8577-92 (Journal)
- Registered Authors
- Kitambi, Satish Srinivas
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacokinetics*
- Antineoplastic Agents/pharmacology*
- Brain Neoplasms/drug therapy*
- Brain Neoplasms/pathology
- Cell Death/drug effects
- Cell Line, Tumor
- Glioblastoma/drug therapy*
- Glioblastoma/pathology
- Humans
- Mice
- Models, Molecular
- Piperidines/pharmacokinetics*
- Piperidines/pharmacology*
- Quinolines/pharmacokinetics*
- Quinolines/pharmacology*
- Stereoisomerism
- Zebrafish
- PubMed
- 27607569 Full text @ J. Med. Chem.
Citation
Hammarström, L.G., Harmel, R.K., Granath, M., Ringom, R., Gravenfors, Y., Färnegårdh, K., Svensson, P.H., Wennman, D., Lundin, G., Roddis, Y., Kitambi, S.S., Bernlind, A., Lehmann, F., Ernfors, P. (2016) The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features. Journal of medicinal chemistry. 59:8577-92.
Abstract
Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping