PROTAC SKP2 Degrader-1

PROTAC SKP2 Degrader-1 is a PROTAC degrader targeting SKP2, with a K d value of 6.28 μM. PROTAC SKP2 Degrader-1 induces targeted degradation of SKP2 via the ubiquitin-proteasome system. PROTAC SKP2 Degrader-1 stabilizes the expression of SOCS1 and regulates the expression of immunoproteasomes through the JAK/STAT pathway, thereby inhibiting tumor cell proliferation. PROTAC SKP2 Degrader-1 is applicable for cancer-related research ^[1]. (Pink: Skp2 ligand; Blue: VHL ligand; Black: linker ).

In Vivo, PROTAC SKP2 Degrader-1 (10-40 mg/kg; i.p.; daily; 14 days) dose-dependently inhibits subcutaneous Jurkat xenograft tumor growth in female NCG mice^[1].

In Vitro, PROTAC SKP2 Degrader-1 (compound HD15) (48 h) inhibits the proliferation of Jurkat cells with an IC₅₀ value of 0.98 μM^[1]. PROTAC SKP2 Degrader-1 (0.0625-1 μM; 48 h) induces proteasome-dependent degradation of SKP2 in Jurkat cells, with a DC₅₀ of 0.29 μM^[1]. PROTAC SKP2 Degrader-1 (0.0625-1 μM; 48 h) modulates the SOCS1/JAK/STAT1/immunoproteasome axis in Jurkat cells, upregulates SOCS1, inhibits p-STAT1, and downregulates the immunoproteasome subunits PSMB8, PSMB9 and PSMB10 in a concentration-dependent manner^[1]. PROTAC SKP2 Degrader-1 (0-6 μM; 48 h) inhibits DNA synthesis and proliferation in Jurkat and Hut78 cells in a dose-dependent manner^[1]. PROTAC SKP2 Degrader-1 (0.1875-6 μM; 48 h) induces apoptosis in Jurkat cells in a dose-dependent manner^[1].

References:
[1]. Chen L, et al. Natural Product-Inspired PROTACs for Leukemia Therapy: Hederagenin-Driven Targeted Degradation of SKP2. J Med Chem. 2026;69(4):4579-4601.