Reynoso-Moreno I, Tietz S, Vallini E, Engelhardt B, Gertsch J, and Chicca A, Selective Endocannabinoid Reuptake Inhibitor WOBE437 Reduces Disease Progression in a Mouse Model of Multiple Sclerosis. ACS Pharmacol. Transl. Sci, March 2021.
Together with collaborators, the Gertsch group investigated the effect of WOBE437, a prototype of selective endocannabinoid reuptake inhibitors (SERIs), in a clinically relevant mouse model of multiple sclerosis (MS). WOBE437 was able to reduce disease severity and accelerate symptom recovery without the typical side effects induced by other medications such as CB1 receptor agonists. Thus, this study indicates that SERIs could be a therapeutic option to slow MS progression and manage major symptoms.
Kowal J, Ni D, Jackson SM, Manolaridis I, Stahlberg H and Locher KP, Structural basis of drug recognition by the multidrug transporter ABCG2. Journal of Molecular Biology, Available online 8 April 2021,
Thanks to high-resolution insights into the cryo-EM structures of nanodisc-reconstituted human ABCG2 bound to tariquidar, topotecan and mitoxantrone, K. Locher, H. Stahlberg and collaborators showed that these anticancer drugs interact with key amino acid residues in the binding pocket of ABCG2. The latter is an ATP-binding cassette transporter whose function affects the pharmacokinetics of drugs and contributes to multidrug resistance of cancer cells. The findings of this study provide additional insight into how ABCG2 differentiates between inhibitors and substrates, and may guide the rational design of new modulators and substrates.