Effect of 3-fluorothalidomide and 3-methylthalidomide enantiomers on tumor necrosis factor production and antitumor responses to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).

  title={Effect of 3-fluorothalidomide and 3-methylthalidomide enantiomers on tumor necrosis factor production and antitumor responses to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).},
  author={Francisco Chung and Brian Desmond Palmer and George W. Muller and Hon-Wah Man and Phillip Kestell and Bruce C. Baguley and Lai-Ming Ching},
  journal={Oncology research},
  volume={14 2},
5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is an antivascular drug that induces tumor necrosis factor (TNF) in mice. Thalidomide inhibits TNF induction by DMXAA and also potentiates its antitumor activity. We investigated whether these effects were enantiomer specific, using the R- or S-enantiomers of two nonracemizable thalidomide analogues. Racemic 3-fluorothalidomide (3FThal) and racemic 3-methylthalidomide (3MeThal) were separated into enantiomers of greater than 98% optical purity using… 
Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
The first biological evaluation of fluoro-thalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay is reported.
Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs
This work shows that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors.
Pharmacokinetic evaluation of vadimezan (ASA404, 5,6-dimethylxanthenone-4-acetic acid, DMXAA)
How different scheduling of vadimezan could significantly enhance the anticancer efficacy of this drug in combination with other therapies, especially those that do not require concurrent corticosteroid administration is discussed.
Concise asymmetric synthesis of configurationally stable 4-trifluoromethyl thalidomide.
A reliable asymmetric approach is developed for preparation of hitherto unknown 4-trifluoromethyl-substituted thalidomide in (3S,4R) and (3R,4S) enantiomerically pure forms that may serve as useful lead compounds for the development of a new generation of thalidmide-based pharmaceuticals.
Evaluation of US 2016/0115161 A1: isoindoline compounds and methods of their use
Results of biological tests, which are superior over those of presently used IMIDs lenalidomide and pomalidomides, make these compounds viable leads for future development of new anticancer drugs against blood and solid cancers.
Fluorothalidomide: a characterization of maternal and developmental toxicity in rabbits and mice.
The potential of fluorothalidomide (FTD), the closest structural analog of TD with stable, nonracemizing isomers, as a model compound for studying stereoselectivity in TD teratogenesis is evaluated.
Molecular Mechanisms and Determinants of Species Sensitivity in Thalidomide Teratogenesis
Chemical instability, potent general toxicity and absence of limb bud embryopathies make FTD an unsuitable stereoselective model for TD teratogenesis.
Abstract 930: p38 MAPK is required for the antitumor activity of the vascular disrupting agent DMXAA
It was found that p38 MAPK was critically involved in DMXAA-induced cytoskeleton reorganization in endothelial cells and TNF-α production in macrophages, both of which were essential for DMXaa-induced vascular disruption.
Liquid chromatographic enantioseparation of thalidomide and its derivatives on cyclodextrin-bonded stationary phases
Abstract The chiral separation of three racemic immunomodulatory drugs, thalidomide, pomalidomide and lenalidomide was studied, using three cyclodextrin bonded stationary phases (β-, hydroxypropyl-β-
Efficient asymmetric synthesis of novel 4-substituted and configurationally stable analogues of thalidomide.
The demonstrated conformational stability of these new thalidomide derivatives provides solid experimental evidence for practical feasibility of the approach described here to overcome the inherent problem of configurational instability of thalidmide by introducing an alkyl or aryl group in the C4 position.