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Development of innovative assays and locally acting therapies aiming at critical kinases in hepatic and renal fibrosis


The DIALOK consortium consists of 2 SMEs (situated in The Netherlands and Hungary) and 5 RTDs (situated in The Netherlands, Germany and Spain) and is dedicated to the development of innovative drugs that display a restricted action within specific target cells or organs. Such locally acting drugs will have an improved safety and efficacy, as side-effects in other tissues will be prevented. We will investigate this therapeutic strategy for kinase inhibitors, a class of drugs that has tremendous therapeutic potential but that also is associated with unacceptable side effects. Kinase inhibitors will be conjugated to two classes of carrier systems, directed to either the liver or kidney. By this, we will develop locally acting drugs for the treatment of either hepatic or renal fibrosis. We want to proof this concept in experimental animal models. An important novel aspect of the project is the linker used for coupling of the drug to the carrier. We will employ Kreatech's Universal Linker System (ULS), a novel patented drug-linker which affords straightforward coupling with most kinase inhibitors (broadly applicable) without changing the original drug structure. Another unique property of ULS is that it provides controlled release of the conjugated drug during a period of days, which is of great importance for effectiveness of the delivered drug. In parallel to development of locally acting kinase inhibitors, we will develop novel assays for detecting activation of kinases. Such assays will be of great value to the project, as it will accelerate and strengthen the validation of the kinase inhibitor-based therapeutics. Kreatech's ULS-based (fluorescent) reporter molecules are especially suitable to detect phosphorylated kinase substrates, and thus afford broadly applicable non-radioactive detection of activated kinases, as compared to traditional kinase activity assays which use radiolabeled ATP or phosphoaminoacid-specific antibodies.'

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Participants (6)