Otviciclib is “first and best in class” drug candidate against multiple myeloma and solid tumors. Developed by Vichem Chemie Ltd. and Medical University of Innsbruck, Austria.
- targets CDK1 (29nM), CDK2 (17nM) CDK3 (11nM), CDK5 (6nM), CDK9 (15nM), CDK16 (30nM) and WNT (10nM).
- has a highly attractive target selectivity profile in vitro
- was selected in a phenotypic assay involving cell-cell interactions with the tumor microenvironment after demonstrating its stem cell killing capabilities
- kills tumor cells within their microenvironment with a low nanomolar EC50 without harming the cells in the microenvironment
- displays a big therapeutic window over “normal” cell lines
- is active in mouse models for multiple myeloma
- has high anticancer activity in many cell lines from solid tumors (i.e., colon cancer, glioblastoma, teratoid/rhabdoid tumor)
- is active in mouse models for colorectal cancer (HCT116)
- has oral bioavailability
- has a clear mode of action (caspase dependent cell death at arrest in G2/M transition, repression of Mcl-1)
- kills Bortezomib resistant human cells
- has synergy with Bortezomib in human cells
- shows no acute and negligible chronic toxicity
- is not red flagged in exploratory heart toxicity tests (hERG)
- does not inhibit CYP enzymes