PROTAC XPO1 degrader-1 is a CRBN-recruiting PROTAC degrader of exportin 1 ( XPO1 ), with a DC50 of 23.67 nM. It exerts anti-proliferative effects against acute myeloid leukemia cells by inducing XPO1 protein degradation, inhibiting NF- κ B activity, inducing apoptosis, and causing G1 cell cycle arrest. PROTAC XPO1 degrader-1 can be used for research on acute myeloid leukemia [1]. (Pink: CRM1 ligand; Blue: Cereblon ligand; Black: linker ).
In Vivo, PROTAC XPO1 degrader-1 (compound 2c (1.0-10 mg/kg; intravenous injection, oral administration; single dose)) exhibits desirable half-lives via both intravenous and oral routes in healthy male Sprague-Dawley rats, but shows low oral bioavailability of only 9.51%[1].
In Vitro, PROTAC XPO1 degrader-1 (compound 2c) (72 h) potently inhibits the proliferation of MV4-11 cells with an IC50 of 0.142 μM; it also inhibits the proliferation of MOLM-13 cells with an IC50 of 0.186 μM[1]. PROTAC XPO1 degrader-1 (5-500 nM; 12 h) induces concentration-dependent degradation of XPO1 in MV4-11 cells, with a DC50 of 23.67 nM; near-complete degradation is achieved within 12 h at a concentration of 100 nM, without altering the mRNA level of XPO1[1]. PROTAC XPO1 degrader-1 (100 nM; 12 h) mediates the degradation of XPO1 in MV4-11 cells via the CRBN-dependent proteasomal pathway[1]. PROTAC XPO1 degrader-1 (200 nM; 24 h) induces apoptosis in 71.4% of MV4-11 cells[1]. PROTAC XPO1 degrader-1 (100-500 nM; 24 h) induces concentration-dependent activation of caspase-3/7 in MV4-11 cells[1]. PROTAC XPO1 degrader-1 (100-200 nM; 24 h) induces concentration-dependent G1 phase arrest in MV4-11 cells, increasing the proportion of G1 phase cells to 60.28%[1]. PROTAC XPO1 degrader-1 (200 nM; 24 h) inhibits TNF-α-induced NF-κB activation by 72% in MV4-11 cells[1]. PROTAC XPO1 degrader-1 (50 nM; 24 h) reduces the migration rate of MV4-11 cells by 42.6%[1].
References:
[1]. Chen G, et al. Discovery of novel XPO1 PROTAC degraders for the treatment of acute myeloid leukemia. European journal of medicinal chemistry. 2025 Feb 05;283:117182.
In Vivo, PROTAC XPO1 degrader-1 (compound 2c (1.0-10 mg/kg; intravenous injection, oral administration; single dose)) exhibits desirable half-lives via both intravenous and oral routes in healthy male Sprague-Dawley rats, but shows low oral bioavailability of only 9.51%[1].
In Vitro, PROTAC XPO1 degrader-1 (compound 2c) (72 h) potently inhibits the proliferation of MV4-11 cells with an IC50 of 0.142 μM; it also inhibits the proliferation of MOLM-13 cells with an IC50 of 0.186 μM[1]. PROTAC XPO1 degrader-1 (5-500 nM; 12 h) induces concentration-dependent degradation of XPO1 in MV4-11 cells, with a DC50 of 23.67 nM; near-complete degradation is achieved within 12 h at a concentration of 100 nM, without altering the mRNA level of XPO1[1]. PROTAC XPO1 degrader-1 (100 nM; 12 h) mediates the degradation of XPO1 in MV4-11 cells via the CRBN-dependent proteasomal pathway[1]. PROTAC XPO1 degrader-1 (200 nM; 24 h) induces apoptosis in 71.4% of MV4-11 cells[1]. PROTAC XPO1 degrader-1 (100-500 nM; 24 h) induces concentration-dependent activation of caspase-3/7 in MV4-11 cells[1]. PROTAC XPO1 degrader-1 (100-200 nM; 24 h) induces concentration-dependent G1 phase arrest in MV4-11 cells, increasing the proportion of G1 phase cells to 60.28%[1]. PROTAC XPO1 degrader-1 (200 nM; 24 h) inhibits TNF-α-induced NF-κB activation by 72% in MV4-11 cells[1]. PROTAC XPO1 degrader-1 (50 nM; 24 h) reduces the migration rate of MV4-11 cells by 42.6%[1].
References:
[1]. Chen G, et al. Discovery of novel XPO1 PROTAC degraders for the treatment of acute myeloid leukemia. European journal of medicinal chemistry. 2025 Feb 05;283:117182.