title: The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101.
abstract: Chemotherapy may still be an essential component to treat cancer in combination with new targeted therapies. But chemotherapy needs to get smarter in order to make those combination regimens more effective and also more tolerable, particularly for an aging population. We describe the first time the synthesis and pharmacological testing of a fusion molecule comprising of the alkylator bendamustine and the HDAC-inhibitor vorinostat. The drug was designed to allow for the exploitation of both mechanisms of action simultaneously with the goal to provide a molecule with superior efficacy over the single agents. The pharmacological testing confirms the full functional capacity of both moieties and encouraging pharmacological data raises the hope that the drug may turn out to be a great addition to the armentarium of anticancer agents.
authors.affiliation: Thomas Mehrling, Mundipharma-EDO GmbH, St. Alban Rheinweg 74, 4052 Basel, Switzerland. Thomas.mehrling@mundipharma-edo.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mehrling
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000069461:Bendamustine Hydrochloride / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001562:Benzimidazoles; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000609929:tinostamustine; D000077337:Vorinostat; D000069461:Bendamustine Hydrochloride; D006655:Histone Deacetylases