The present invention provides nine selective c-FLIP inhibitors that are useful in the treatment of cancer, alone or in combination with other chemotherapeutic agents, in particular with TRAIL-based chemotherapeutic agents. The present invention also relates to pharmaceutical compositions and kits comprising at least one of the nine selective c-FLIP inhibitors and their use in methods for the treatment of cancer, in particular to overcome chemoresistance or to improve sensitivity of tumors to TRAIL-based therapy.
