PROTAC PTPN2 degrader-1

PROTAC PTPN2 degrader-1 (example77) (1 nM-10 μM; 24 h) HiBiT degradation assay conducted in 293T cells stably expressing HiBiT-tagged human PTPN2 shows that the compound has a DC₅₀ of 18 nM and a Dmax of 92% after 24-hour treatment with maximal degradation reached at 100 nM, there is no hook effect and negligible cellular toxicity at 10 μM, which demonstrates that Example 77 exhibits potent nanomolar PTPN2 degradation with a wide working window and no protein rebound at high concentrations^[1].
PROTAC PTPN2 degrader-1 (10-100 nM; 24 h) shows PTPN2 degradation that is independently confirmed by Western blot^[1].
PROTAC PTPN2 degrader-1 (1 nM-10 μM; 30 min) spectrophotometric enzymatic inhibition assay using recombinant human PTPN2 and PTP1B proteins shows that it delivers an IC₅₀ of 22 nM for PTPN2 and an IC₅₀ higher than 1.2 μM for homologous PTP1B with a selectivity index SI of approximately 54, which proves that Example 77 exerts minimal inhibitory activity against homologous PTP1B and possesses excellent target selectivity^[1].
PROTAC PTPN2 degrader-1 (10-100 nM; 72 h) degrades PTPN2, thereby relieving the negative regulation of the IFNγ pathway and significantly enhancing the anti-proliferative effect of interferon on B16F10 murine melanoma^[1].
PROTAC PTPN2 degrader-1 (100 nM; 24 h) exerts immunopotentiating effect via upregulating IFN pathway transcription in B16F10 cells^[1].
ROTAC PTPN2 degrader-1 (100 nM; 48 h) promotes T cell activation and effector cytokine secretion to strengthen anti-tumor immunity^[1].
ROTAC PTPN2 degrader-1 (1 μM; 10-60 min) exhibits good metabolic stability in mouse liver microsomes, with 71% of the drug remaining after a 60-minute incubation and a low in vitro clearance rate^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.