Compounds for disrupting microtubule networks and mitosis in brain cancer

 Project ID: D2014-42

Background

Primary brain tumors and secondary intracranial tumors from metastatic spread of other cancers (e.g., melanoma, lung carcinoma) have been inaccessible to therapy with microtubule-targeted agents (vincristine, vinblastine, paclitaxel) because the latter do not readily cross the blood-brain barrier.

Invention Description

Researchers from the University of Toledo have developed novel microtubule-targeted compounds that can effectively cross the blood brain barrier. Lab studies have shown the compounds inhibit Progression of Subcutaneous and Intracerebral Glioma Xenografts in Mice.

Applications

• Brain metastases

Advantages

• Can cross the blood brain barrier

IP Status:                          Issued US Patents: 9,023,871 and 9,061,994

Publications:       

1. Maltese W, et al. 6-MOMIPP, a novel brain-penetrant anti-mitotic indolyl-chalcone, inhibits glioblastoma growth and viability.  Cance Chemother Pharmacol. 2019 Feb;83(2):237-254.  
2. Trabbic C J, et al., Synthesis and Biological Evaluation of Isomeric Methoxy Substitutions on Anti-Cancer Indolyl-Pyridinyl-Propenones: Effects on Potency and Mode of Activity. Eur J Med Chem. 2016 October 21; 122: 79–91.
3.   Trabbic C, et al., Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity. J Med Chem.     2015      Mar 12;58(5):2489-512.
4.  Robinson M W, et al., Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of non-apoptotic cell death. J Med   Chem.2012   March 8; 55(5): 1940–1956.