CAAI - Covalent-allosteric AKT inhibitors
Inhibitors of the AKT pathway with a new mode of binding
The development of new drugs in oncology has shifted from unspecific cytotoxic drugs to highly specific substances with known targets and modes of action. A prominent group of these target specific cancer drugs are the kinase inhibitors.
The invented substances are inhibitors of the kinase AKT which is involved in several pathways regulating cell functions in cancer, e.g. survival and proliferation. The particular novelty of the invented compounds is based on their combined covalent-allosteric binding mode. These are first-in-class modulators of AKT with a novel mode of inhibition. Covalent-allosteric inhibitors show extended drug-target residence times.
- AKT inhibitors with a new mode of action
- The inhibitors bind AKT irreversibly and specifically with highest affinity
Scope of application
AKT is a serine/threonine kinase and oncogene that has already been identified and addressed as a target in cancer therapy by several pharma companies. The invented substances are of high interest for any pharma company with an oncology pipeline and are of special advantage for those who seek to improve, broaden or supplement their kinase inhibitor portfolio.
Binding specificity as well as an IC50 of 0.2 nM for the most promising compound have been determined by in vitro experiments so far. On behalf of the Technical University (TU) of Dortmund, PROvendis offers access to rights for commercial use as well as the opportunity for further co-development. In case of interest we will be pleased to inform you about the patent status.
Publications & Links
Weisner J, et al. (2015) Covalent-allosteric kinase inhibitors. Angewandte Chemie, DOI: 10.1002/anie.201502142R1.
Vivanco I, et al. (2014) A kinase-independent function of AKT promotes cancer cell survival. eLife 31:3.
Barf T & Kaptein A (2012) Irreversible protein kinase inhibitors: balancing the benefits and risks. J. Med. Chem. 55: 6243-62.
Hers I, et al. (2011) Akt signaling in health and disease. Cell. Signal. 23: 1515-27.
Garcia-Echeverria C & Sellers WR (2008) Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene 27: 5511-26.
Keywordssmall kinase inhibitor, cancer therapy
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