HP211206 is a bifunctional CRBN -recruiting SARS-CoV-2 M pro PROTAC degrader with a CRBN IC50 of 3.2 μM and a SARS-CoV-2 M pro DC50 of 621 nM. HP211206 recruits E3 ubiquitin ligase CRBN to drive ubiquitination and proteasomal degradation of wild-type SARS-CoV-2 M pro and E166 mutant while inhibiting M pro enzymatic activity, exhibits no cytotoxicity against normal mammalian cells at tested concentrations, and can be used for the study of COVID-19 and SARS-CoV-2 infection [1] (Pink: SARS-CoV-2 Mpro ligand; Blue: Cereblon ligand; Black: linker ).
In Vitro, HP211206 (1 nM-100 μM; 30 min) strongly inhibits purified SARS-CoV-2 Mpro with an IC50 of 181.9 nM and binds CRBN with an IC50 of 3.2 μM[1]. HP211206 (3 nM-10 μM; 2-48 h) induces time- and dose-dependent degradation of wild-type SARS-CoV-2 Mpro in HEK 293T cells, with a DC50 of 621 nM[1]. HP211206 (10-3000 nM; 2-48 h) induces dose-dependent degradation of drug-resistant SARS-CoV-2 Mpro mutants SARS-CoV-2 MproE166V and SARS-CoV-2 MproE166A in HEK 293T cells[1]. HP211206 (3 nM-10 μM; 2-48 h) dose-dependently and time-dependently degrades SARS-CoV-2 Mpro in transfected HEK 293T cells[1]. HP211206 (Serially diluted concentrations; 3 h) binds to GST-tagged wild-type human Cereblon with an IC50 of 3.2 μM[1]. HP211206 (0.1-100 μM; 48 h) shows no significant cytotoxicity in HEK 293T cells at concentrations up to 100 μM after 48 h of incubation[1].
References:
[1]. Sang X, et al. A Chemical Strategy for the Degradation of the Main Protease of SARS-CoV-2 in Cells. Journal of the American Chemical Society. 2023 Dec 20;145(50):27248-27253.
In Vitro, HP211206 (1 nM-100 μM; 30 min) strongly inhibits purified SARS-CoV-2 Mpro with an IC50 of 181.9 nM and binds CRBN with an IC50 of 3.2 μM[1]. HP211206 (3 nM-10 μM; 2-48 h) induces time- and dose-dependent degradation of wild-type SARS-CoV-2 Mpro in HEK 293T cells, with a DC50 of 621 nM[1]. HP211206 (10-3000 nM; 2-48 h) induces dose-dependent degradation of drug-resistant SARS-CoV-2 Mpro mutants SARS-CoV-2 MproE166V and SARS-CoV-2 MproE166A in HEK 293T cells[1]. HP211206 (3 nM-10 μM; 2-48 h) dose-dependently and time-dependently degrades SARS-CoV-2 Mpro in transfected HEK 293T cells[1]. HP211206 (Serially diluted concentrations; 3 h) binds to GST-tagged wild-type human Cereblon with an IC50 of 3.2 μM[1]. HP211206 (0.1-100 μM; 48 h) shows no significant cytotoxicity in HEK 293T cells at concentrations up to 100 μM after 48 h of incubation[1].
References:
[1]. Sang X, et al. A Chemical Strategy for the Degradation of the Main Protease of SARS-CoV-2 in Cells. Journal of the American Chemical Society. 2023 Dec 20;145(50):27248-27253.