Abstract: The present invention provides methods of negatively modulating the Werner protein (WRN) to inhibit proliferative cells characterized by high microsatellite instability (MSI-H), for example to treat proliferative diseases (such as cancer) characterized by high MSI (MSI-H). Further provided are compositions used in such methods.

Abstract: Disclosed inter alia is the use of certain chromenone derivatives, which are modulators of a mitotic kinesin such as KSP, in the treatment of cellular proliferative diseases. The chromenones derivatives are administered with another chemotherapeutic agent selected from neutropenia treatment agents, alkylating agents, antimetabolites, platinating agents, topoisomerase inhibitors, tubulin agents and signalling inhibitors (e.g., kinase inhibitors). Pharmaceutical compositions comprising one or both types of active agents are also disclosed.