A Proven Technology Platform
New Kinase inhibitor (in vivo active) for autoimmune disease application, a patent was filled by the client.
In this program, by using our HitFast Discovery® platform, we assisted in the identification and optimization of a novel series which inhibits the kinase of interest. This was done by designing and synthesizing 80 molecules. The hits (10 molecules) were then taken into the second iteration of Optima Lead® to improve their affinity and to explore better their SAR. The synthesis of 50 molecules around the hit series resulted in an improved IC50 which passed from 2 uM to 100 nM. In a third iteration, the selectivity of lead compounds issues was investigated by designing and synthesizing 50 molecules. The lead optimization phase resulted in a selective lead series showing an activity (IC50 = 2 nM) toward the kinase of interest 100 folds higher than in the other kinases.
New CETP/PLTP inhibitor (in vivo active) for cardiovascular disease application, the molecule will be acquired by a big Pharma.
In this lead identification and optimization cardiovascular program, in collaboration with Dr. Karim Berrada (Director of Drug Discovery) at Ingenious targeting Laboratories (Stony Brook, NY, USA), we have identified and characterized a novel class of dual-inhibitors for both PLTP and CETP, using PLTP and CETP 3-D models based on PLTP homologues and CETP X-ray structure respectively. While there are no known PLTP inhibitors, the lead compounds present a different binding model than all known CETP inhibitors, and occupy a new chemical space to all known CETP inhibitors. In vivo validation of these dual-inhibitors demonstrates that they inhibit both PLTP and CETP equipotently and reduce cholesterol in plasma. Subsequent studies indicate that these compounds are drug-like and safe.
New Kinase inhibitor (in vivo active) proof of concept of our technology platform, a patent was filled.
In this project, OriBase Pharma scientists identified and optimized two novel lead series with an in vitro and in vivo proof of concept. The identified lead series are strong inhibitors of BCR-ABL kinase in its wild type and mutated form mainly the T315I mutation. This is one of the most promising proofs of concept of the OriBase Pharma technology platforms, HitFast Discovery® and Selective Lead. The lead series are now under extensive investigations in the regulatory preclinical phase for the treatment of human chronic myeloid leukemia in its normal and Imatinib resistant forms.