Research topics of the team
Team Medicinal chemistry and translational research
(MCTR) is an Inserm team U1268 (started on 1st January 2019) and is a part of the Unit UMR8038 CitCoM.
Our project focuses on medicinal chemistry and translational research in order to validate new therapeutic targets, to design novel modulators (hits/leads), and to study responses of targeted therapies in clinics thanks to strong collaborations and to our hospital practitioners within the biology platform of the Cochin hospital. We manly focus on development of innovative anticancer strategies targeting the progress of tumors and angiogenesis. Our research is at interface of chemistry and biology and we employ various and complementary methodologies: in silico modeling, medicinal chemistry, bioassays, hit-to-lead optimization. Our final goal is to develop original and efficient hit/lead molecules with opportunities to obtain patents and to valorize them in an industrial transfer and clinics applications.
Theme 1. Development of anticancer hit/lead molecules
We develop enzyme inhibitors and modulators of protein-protein interactions involved in cancer to target the progress of tumors and angiogenesis using rational drug design and in vitro screening supported by molecular modeling and in silico screening. We prioritize biologically validated targets with available structural data: VEGFR, SIRT1, thymidine phosphorylase and estrogen receptor ERa. The modulation of some targets with not resolved structure, such as GPER, is also explored. The team has a particular expertise in the synthesis of heterocycles and peptides. In vivo biological essays are performed in collaboration with pharmacology teams.
Theme 2. In silico screening and ADME-Tox prediction
We develop and perform methods/tools for in silico screening and rational drug design focusing on anticancer protein targets studied by the team. In addition, we perform in silico ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) prediction in order to further optimize our hit molecules. We develop a new software DrugME for prediction of drug-drug interactions due to inhibition of key drug metabolizing enzymes (ME) as cytochrome P450 and sulfotransferases, and ABC transporters as well.
Theme 3. Translational research: response biomarkers on targeted therapy on clinic
We perform biomarkers research of either response or toxicity of targeted therapies on patients with cancer (non small cell lung cancer) at the department of cancerology in Cochin hospital (Pr F Goldwasser). This work has been done thanks to our strong collaboration with the “Drug Biology – Toxicology” Unit in Cochin hospital (Pr X Decleves). These cancers can be treated by either kinase inhibitors or by antibodies targeting the immune system, used for example in lung or renal cancers. Our practitioners in Cochin hospital are specialized on both kinases inhibitors and antibodies, including their dosage (therapeutic drug monitoring), but also the search of response and/or toxicity biomarkers. We work to optimize potential synergistic effects of different conceived molecules thanks to transduction pathways knowledge.