Accueil > Départements scientifiques > Département TERI > Petites molécules pour cibles biologiques
Petites molécules pour cibles biologiques
Objectifs
Notre équipe conçoit, synthétise et évalue des petites molécules inhibiteurs ou modulateurs de cibles biologiques. Notre méthodologie repose sur une approche rationnelle, incluant la dynamique moléculaire, le criblage virtuel, la chimie médicinale, les techniques biophysiques (RMN, TSA…) et la biologie structurale. Nous utilisons ces petites molécules comme outils pour explorer les voies biologiques impliquées dans le cancer et/ou ouvrir la voie à de nouveaux thérapeutiques.
Projets
Le canal anionique tensiodépendant VDAC1
VDAC1 est un canal ionique localisé dans la membrane externe des mitochondries, dont la fonction est cruciale pour la survie cellulaire et les voies métaboliques énergétiques. VDAC1 est aussi impliquée dans l’apoptose et pourrait jouer un rôle dans l’invasion des cellules cancéreuses et la formation de métastases. Pour mieux évaluer le rôle de VDAC dans les cellules cancéreuses, et éventuellement valider le ciblage pharmacologique des voies associées, nous cherchons à développer des ligands spécifiques, capables de moduler son activité.
Financements : CNRS, Ligue contre le cancer Haute Savoie, ANR Plascan
La protéine kinase CK2
CK2 est une protéine kinase impliquée dans de nombreuses pathologies, notamment en cancer et les infections virales. La particularité structurale de CK2 est d’exister sous deux formes constitutivement actives (CK2α et CK2α2β2) . Pour mieux comprendre le rôle des différentes formes de CK2 dans le cancer et dans l’infection virale, nous développons des molécules spécifiques ciblant des sites allostériques.
Financements : ANR CK2COV (porteur), ITMO Cancer PCSI (partenaire)
D’autres projets incluent :
- la conception d’inhibiteurs de la pompe d’efflux ABCG2, responsable de la résistance à de multiples anti-cancéreux (mitoxantrone, doxorubicine, camptothécine, méthotrexate…) (Collaboration P. Falson, Lyon).
- le développement du criblage par RMN de fragments contre des GPCR (ANR NanoWAC, Prof. C. Demesmay, ISA, Université Lyon1).
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KRIMM Isabelle
Chef d’Équipe
Chargé de Recherche CNRS
04 78 77 75 86
isabelle.krimm@univ-lyon1.fr
Membres de l'équipe
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GRENIER Dylan
Doctorant - Equipe I Krimm
Publications
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4,5,7-Trisubstituted indeno[1,2-b]indole inhibits CK2 activity in tumor cells equivalent to CX-4945 and shows strong anti-migratory effects
Birus R, El-Awaad E, Ballentin L, Alchab F, Aichele D, Ettouati L, Götz C, Le Borgne M, Jose J FEBS Open Bio
Conformational Diversity Using All-Atom Simulations Provides New Insights into the Structural Origin of the Closed StatesPreto J, Gorny H, Krimm I Int. J. Mol. Sci.
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Brain safety concerns of nanomedicines: The need for a specific regulatory framework
Szabat-Iriaka B, Le Borgne M Drug Discov Today
Broad-Spectrum Anticancer Activity and Pharmacokinetic Properties of a Prenyloxy-Substituted Indeno[1,2- b]indole Derivative, Discovered as CK2 InhibitorEl-Awaad E, Birus R, Marminon C, Bouaziz Z, Ballentin L, Aichele D, Le Borgne M, Jose J Pharmaceuticals (Basel)
Targeting netrin-3 in small cell lung cancer and neuroblastomaJiang S, Richaud M, Vieugué P, Rama N, Delcros JG, Siouda M, Sanada M, Redavid AR, Ducarouge B, Hervieu M, Breusa S, Manceau A, Gattolliat CH, Gadot N, Combaret V, Neves D, Ortiz-Cuaran S, Saintigny P, Meurette O, Walter T, Janoueix-Lerosey I, Hofman P, Mulligan P, Goldshneider D, Mehlen P, Gibert B EMBO Mol Med
The intrinsically disordered N-terminus of the voltage-dependent anion channelPreto J, Krimm I PLoS Comput Biol
Uncompetitive nanomolar dimeric indenoindole inhibitors of the human breast cancer resistance pump ABCG2Guragossian N, Belhani B, Moreno A, Nunes MT, Gonzalez-Lobato L, Marminon C, Berthier L, Rocio Andrade Pires AD, Özvegy-Laczka C, Sarkadi B, Terreux R, Bouaziz Z, Berredjem M, Jose J, Di Pietro A, Falson P, Le Borgne M Eur J Med Chem
Ninhydrins inhibit carbonic anhydrases directly binding to the metal ionBouzina A, Berredjem M, Nocentini A, Bua S, Bouaziz Z, Jose J, Le Borgne M, Marminon C, Gratteri P, Supuran C European Journal of Medicinal Chemistry
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Synthesis, optimization, antifungal activity, selectivity, and CYP51 binding of new 2-aryl-3-azolyl-1-indolyl-propan-2-ols
Lebouvier N, Pagniez F, Na YM, Shi D, Pinson P, Marchivie M, Guillon J, Hakki T, Bernhardt R, Yee SW, Simons C, Lézé MP, Hartmann RW, Mularoni A, Le Baut G, Krimm I, Abagyan R, Le Pape P, Le Borgne M Pharmaceuticals
Comparative Analysis, Structural Insights, and Substrate/Drug Interaction of CYP128A1 in Mycobacterium tuberculosisNgcobo NS, Chiliza ZE, Chen W, Yu JH, Nelson DR, Tuszynski JA, Preto J, Syed K Int J Mol Sci .
Fragment linking strategies for structure-based drug designBancet A, Raingeval C, Lomberget T, Le Borgne M, Guichou JF, Krimm I J Med Chem
Blocking SHH/patched interaction triggers tumor growth inhibition through patched-induced apoptosisBissey PA, Mathot P, Guix C, Jasmin M, Goddard I, Costechareyre C, Gadot N, Delcros JG, Mali SM, Fasan R, Arrigo AP, Dante R, Ichim G, Mehlen P, Fombonne J: Cancer research
Synthesis, biological evaluation and molecular docking studies of new amides of 4-chlorothiocolchicine as anticancer agentsKlejborowska G, Urbaniak A, Maj E, Preto J, Moshari M, Wietrzyk J, Tuszynski JA, Chambers TC, Huczyński A Bioorganic Chemistry
Improved surface display of human Hyal1 and identification of testosterone propionate and chicoric acid as new inhibitorsLengers I, Herrmann F, Le Borgne M, Jose J Pharmaceuticals
Investigation of the electrical properties of microtubule ensembles under cell-like conditionsKalra AP, Patel SD, Bhuiyan AF, Preto J, Scheuer KG, Mohammed U, Lewis JD, Rezania V, Shankar K, Tuszynski JA Nanomaterials
Synthesis of new piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of Candida albicans multidrug transporters by a Buchwald-Hartwig cross-coupling reactionGuillon J, Nim S, Moreau S, Ronga L, Savrimoutou S, Thivet E, Marchivie M, Di Pietro A, Prasad R, Le Borgne M RCS Advances
Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agentPagniez F, Lebouvier N, Na YM, Ourliac-Garnier I, Picot C, Le Borgne M, Le Pape P J Enzyme Inhib Med Chem.
The discovery of naphtho[2,3-b]furane-4,9-dione as new backbone for the development of active CK2 inhibitors via a molecular modeling approach using indeno[1,2-b]indole entityHaidar S, Marminon C, Aichele D, Nacereddine A, Zeinyeh W, Bouzina A, Berredjem M, Ettouati L, Bouaziz Z, Le Borgne M, Jose J Molecules
Synthesis, antiproliferative activity and molecular docking studies of 4-chlorothiocolchicine analoguesKlejborowska G, Moshari M, Maj E, Majcher U, Preto J, Wietrzyk J, Tuszynski JA, Huczyński A Chem Biol Drug Des
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Synthesis, biological evaluation and molecular docking studies of new amides of 4-bromothiocolchicine as anticancer agents
Klejborowska G, Urbaniak A, Preto J, Maj E, Moshari M, Wietrzyk J, Tuszynski JA, Chambers C, Huczyński A Bioorganic & Medicinal Chemistry
1D NMR WaterLOGSY as an efficient method for fragment-based lead discoveryRaingeval C, Cala O, Brion B, Le Borgne M, Hubbard RE, Krimm I J Enzyme Inhib Med Chem
In vitro modulation of multidrug resistance by pregnane steroids and in vivo inhibition of tumour development by 7α-OBz-11α(R)-OTHP-5β-pregnanedione in K562/R7 and H295R cell xenograftsAlameh G, Emptoz-Bonneton A, Rolland de Ravel M, Matera EL, Mappus E, Balaguer P, Rocheblave L, Lomberget T, Dumontet C, Le Borgne M, Pugeat M, Grenot C, Cuilleron CY J Enzyme Inhib Med Chem .
Discovery of holoenzyme-disrupting chemicals as substrate-selective CK2 inhibitorsKufareva I, Bestgen B, Brear P, Prudent R, Laudet B, Moucadel V, Ettaoussi M, Sautel CF, Krimm I, Engel M, Filhol O, Borgne ML, Lomberget T, Cochet C, Abagyan R Scientific Reports
Fgd5 is a Rac1-specific Rho GEF that is selectively inhibited by aurintricarboxylic acidPark S, Guo Y, Negre J, Preto J, Smithers CC, Azad AK, Overduin M, Murray AG, Eitzen G Small GTPases .
Assessing and improving the performance of consensus docking strategies using the DockBox packagePreto J, Gentile F J Comput Aided Mol Des .
Carbazole scaffolds in cancer therapy: a review from 2012-2018Issa S, Prandina A, Bedel N, Rongved P, Yous S, Le Borgne M, Bouaziz Z J Enzyme Inhib Med Chem.
NMR investigation of protein-ligand interactions for G-protein coupled receptorsRaingeval C, Krimm I Future Med Chem
A comparative adsorption study of benzophenone-3 onto synthesized lipophilic organosilicate, Laponite and montmorilloniteCharaabi S, Tchara L, Marminon C, Bouaziz Z, Holtzinger G, Pensé-Lhéritier AM, Le Borgne M, Issa S Applied Clay Science
Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitorsPrandina A, Radix S, Le Borgne M, Jordheim LP, Bousfiha Z, Fröhlich C, Samuelsen Ø, Frøvold E, Rongved P, Åstrand OAH Tetrahedron
Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitorsKildahl-Andersen G, Schnaars C, Prandina A, Radix S, Le Borgne M, Jordheim LP, Gjøen T, Andresen AMS, Lauksund S, Fröhlich C, Samuelsen Ø, Rongved P, Åstrand OAH Medchemcomm .
Behaviour of tetrabenazine in acid medium: Reassessment and impact on formulationEttouati L, Senta-Loys Z, Bourgeois S, Fenet B, Le Borgne M, Fessi H Pharmaceutics.
Comparison of SEC and AF4 analytical tools for size estimation of typhoid Vi polysaccharidesBayart C, Jean E, Paillagot M, Renoud A, Raillard A, Paladino J, Le Borgne M Analatycal Methods
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Inhibition of Shiga toxin-converting bacteriophage development by novel antioxidant compounds
Sylwia Bloch S, Bożena Nejman-Faleńczyk B, Karolina Pierzynowska K, Ewa Piotrowska E, Alicja Węgrzyn A, Marminon C, Bouaziz Z, Nebois P, Jose J, Le Borgne M, Saso L, Węgrzyn G J Enzyme Inhib Med Chem .
N,N’-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity against overexpressing NorA efflux pump Staphylococcus aureus 1199B strainsRadix S, Jordheim AD, Rocheblave L, N'Digo S, Prignon AL, Commun C, Michalet S, Dijoux-Franca MG, Mularoni A, Walchshofer N
Ultrasound molecular imaging as a non-invasive companion diagnostic for netrin-1 interference therapy in breast cancerWischhusen J, Wilson KE, Delcros JG, Molina-Peña R, Gibert B, Jiang S, Ngo J, Goldschneider D, Mehlen P, Willmann JK, Padilla F Theranostics
Synthesis and preclinical evaluation of TPA-based zinc chelators as metallo-β-lactamase inhibitorsSchnaars C, Kildahl-Andersen G, Prandina A, Popal R, Large Radix S, Le Borgne M, Gjøen T, Andresen AMS, Heikal A, Økstad OA, Fröhlich C, Samuelsen Ø, Lauksund S, Jordheim LP, Rongved P, Åstrand OAH ACS Infect Dis
Structure-based design and profiling of novel 17β-HSD14 inhibitorsBraun F, Bertoletti N, Möller G, Adamski J, Frotscher M, Guragossian N, Patrícia Gírio PA, Le Borgne M, Ettouati L, Falson P, Müller S, Vollmer G, Heine A, Klebe G, Marchais-Oberwinkler S Eur J Med Chem .
Synthesis, X-ray structure, in silico calculation, and carbonic anhydrase inhibitory properties of benzylimidazole metal complexesBouchouit M, Bouacida S, Zouchoune B, Merazig H, Bua S, Bouaziz Z, Le Borgne M, Supuran CT, Bouraiou A J Enzyme Inhib Med Chem.
Synthesis, spectroscopic characterization, and in vitro antibacterial evaluation of novel functionalized sulfamidocarbonyloxyphosphonatesBouzina A, Bechlem K, Berredjem H, Belhani B, Becheker I, Lebreton J, Le Borgne M, Bouaziz Z, Marminon C, Berredjem M Molecules
Enhancement of iodinin solubility by encapsulation into cyclodextrin nanoparticlesPrandina A, Herfindal L, Radix S, Rongved P, Døskeland S, Le Borgne M, Perret F
Self-assembled supramolecular nanoparticles improve the cytotoxic efficacy of CK2 inhibitor THN7Nacereddine A, Bollacke A, Roka E, Marminon C, Bouaziz Z, Fenyvesi F, Bácskay I, Jose J, Perret F, Le Borgne M Pharmaceuticals