GSPT1 degrader-1

GSPT1 Degrader-1 (Compound 9q) effectively facilitates the degradation of G1 to S phase transition 1 (GSPT1) through the ubiquitin-proteasome system and induces G0/G1 phase arrest and apoptosis in cells [1].

PROTAC GSPT1 degrader-1 (Compound F) is a PROTAC-based degrader that effectively targets and degrades G1 to S phase transition protein 1 (GSPT1), achieving degradation rates of 95% at 1 μM and 86% at 0.1 μM. Additionally, this compound inhibits the viability of HL-60 cells with an IC50 of 9.2 nM.

PROTACFLT3/GSPT1/IKZF1/3 degrader-1 is an FLT3 PROTAC degrader with DC50 = 1.2 nM. It functions as a molecular glue to degrade its brain substrates and exhibits antiproliferative activity against resistant acute myeloid leukemia (AML) cells, showing potential applications in AML research.

SJ6986 is a potent, selective, and orally active GSPT1/2 degrader, effectively degrading GSPT1 with a DC50 of 2.1 nM (D max 99%) [1].

DP-15 acts as a degrader of GSPT1 and BRD4, with DC50 values of 5.25 nM and 0.48 nM, respectively. This compound exhibits antiproliferative activity in AML and NHL cells, showing IC50 values in the nanomolar range, induces G1 phase cell cycle arrest, and triggers apoptosis in MOLM13 cells. Additionally, DP-15 demonstrates anti-leukemic properties in the MOLM-13 xenograft mouse model. [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonThalidomide-5-OH]

LYG-409 is an orally active GSPT1 degrader. It demonstrates exceptional in vivo anti-tumor activity against acute myeloid leukemia and prostate cancer, with tumor growth inhibition rates (TGI) of 94.34% and 104.49%, respectively. LYG-409 inhibits KG-1 cells by degrading GSPT1, with an IC50 of 9.50 nM and a DC50 of 7.87 nM in vitro.

SJ988497 is a PROTAC JAK2 degrader that effectively inhibits proliferation in CRLF2-rearranged (CRLF2r) cells and facilitates the degradation of the CRBN neosubstrate GSPT1. Composed of a Ruxolitinib derivative, a linker, and the CRBN ligand Pomalidomide, SJ988497 is utilized in researching acute lymphoblastic leukemia (ALL) [1].

MDEG-541 is a potent MYC-MAX degrader that exhibits antiproliferative activity by downregulating the expression of GSPT1, MYC, GSPT2, and PLK1 proteins [1].

GBD-9, a dual-mechanism degrader, effectively promotes the degradation of BTK and GSPT1 through recruitment of E3 ligase cereblon (CRBN). As a PROTAC molecule, GBD-9 induces BTK degradation, while also acting as a molecular glue for GSPT1 degradation, demonstrating potent inhibition of cancer cell growth [1].

GSPT1 degrader-2 is a potent degrader of GSPT1 [1].