Evaluation of US 2016/0115161 A1: isoindoline compounds and methods of their use

ABSTRACT

Introduction: Immunomodulatory drugs (IMIDs®) are small orally available molecules that modulate the immune system and other biological targets through multiple mechanisms of action and have been successfully used in the treatment of myelodysplastic syndrome and multiple myeloma. However, recent studies of their complex mechanism of action revealed their potential in autoimmune diseases and solid tumors, which intensified scientific interest in these compounds.

Areas covered: This patent application claims new IMIDs for the treatment of cancer and disorders associated with angiogenesis and inflammation. Substitution of isoindolinone ring on position 5 with urea and amide linkers connected to different aromatic rings lead to very potent inhibitors of TNF-α production with antiproliferative activities against Nemalwa cells and against colorectal, pancreatic, prostate and breast cancer cell lines in sub-nano to low-nanomolar concentration range.

Expert opinion: Substitution of position 5 on the isoindolinone ring, which is presented in this invention, is currently the hot spot of Celgene’s research. Results of biological tests, which are superior over those of presently used IMIDs lenalidomide and pomalidomide, make these compounds viable leads for future development of new anticancer drugs against blood and solid cancers.

KEYWORDS:

• Cancer
• cereblon
• IMIDs
• immunomodulators
• isoindoline
• thalidomide
• TNF-α

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by the Slovenian Research Agency; Javna Agencija za Raziskovalno Dejavnost RS grant number P1-0208.