MSC2530818

In vitro: MSC2530818 binds to CDK8 and CDK19 with similar affinity (4 nM) and shows potent inhibition of phospho-STAT1SER727 in SW620 human colorectal carcinoma cells (IC50=8 +/- 2 nM). It also demonstrates potent inhibition of WNT-dependent transcription in human cancer cell lines that have constitutively activated WNT signaling. MSC2530818 is a soluble CDK8 inhibitor with high permeability and low efflux ratio in Caco-2 cells (ER = 1.5) and does not inhibit any cytochrome P450 subtypes (Cyp IC50s > 20 uM).

In vivo: MSC2530818 shows acceptable pharmacokinetics (PK) in all tested preclinical species (mouse, rat, dog). It demonstrates reduction of tumor growth rates of established human SW620 colorectal carcinoma xenografts.