Bisubstrate-Type Chemical Probes Identify GRP94 as a Potential Target of Cytosine-Containing Adenosine Analogs

Dany Pechalrieu (1) , Fanny Assemat (1) , Ludovic Halby (1, 2) , Marlene Marcellin (3) , Pengrong Yan (4) , Karima Chaoui (3) , Sahil Sharma (4) , Gabriela Chiosis (4) , Odile Burlet-Schiltz (3) , Paola Arimondo (2, 1) , Marie Lopez (5, 1)

1 ETaC - Pharmacochimie de la Régulation Epigénétique du Cancer
2 EpiCBio - Chimie biologique épigénétique - Epigenetic Chemical Biology
3 IPBS - Institut de pharmacologie et de biologie structurale
4 Memorial Sloane Kettering Cancer Center [New York]
5 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest.

Domains: Chemical Sciences; Life Sciences [q-bio]

Dany Pechalrieu, Fanny Assemat, Ludovic Halby, Marlene Marcellin, Pengrong Yan, et al.. Bisubstrate-Type Chemical Probes Identify GRP94 as a Potential Target of Cytosine-Containing Adenosine Analogs. ACS Chemical Biology, 2020, 15 (4), pp.952-961. ⟨10.1021/acschembio.9b00965⟩. ⟨pasteur-03026521⟩