10758

Multi Action Pt(IV) and Anticancer Drugs

Gibson Dan, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

 

Category

LifeSciences and Biotechnology   

Keywords

cancer, chemotherapy, prodrug

Current development stage

For Pharmaceutical development: TRL3 - hypothesis testing and intial POC demonstrated in limited # of in-vitro models

Choose current TRL level

 

Application

Square planar PtII complexes such as cisplatin are widely used today to treat several forms of cancer, alone or in combination with other drugs. Pt drugs suffer from two major problems: the first is the ability of tumors to acquire resistance to these drugs; and the second relates to the dose-limiting side effects that are known to be associated with the chemotherapy.

In order to overcome resistance to a given drug, and diminish its side effects, clinicians have been treating patients with a combination of drugs that have different cellular targets and different modes of action. One of the popular strategies is to use inert, octahedral multi-action PtIV complexes as prodrugs. PtIV complexes are particularity suitable as prodrugs because they are stable outside the cancer cell and become activated by reductive elimination inside the cell. Multi-action PtIV prodrugs are usually prepared by an oxidative addition to the square planar PtII drugs with H2O2 and a subsequent modification of the axial hydroxide ligands.

Our Innovation

The proposed technology is a platform for conjugation of  the Pt to bioactive moieties in a different chemical mode from what has been used until now. This will expand the potential combinations of other drugs to Pt, in a single prodrug, and therefore enable different kinds of of chemotherapy treatment.

In order to enable facile and effective synthesis of novel Pt-based prodrugs, active compounds that do not contain carboxylic acid (or carboxylate) functionalities, the inventors have developed a novel approach for conjugating such molecules via existing hydroxyl groups or amine groups to the axial positions of PtIV compounds. With this approach, the original actives are released following reduction of the PtIV.

Opportunity

Multi-action Pt(IV) anticancer agents almost exclusively tether the Pt only to bioactive ligands which contain carboxylate, thus limiting the scope of potential drugs. The proposed technology suggests a platform for conjugating the Pt to other bioactive moieties which allows combining drugs such as gemcitabine, taxol and estramustine and others, to Pt in a single prodrug.

 

Contact for more information:

Mel Larrosa
VP Business Development Healthcare
+972-2-6586692
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