proteasome-mediated

Dicyclanil is an insect growth regulator with a chemical structure similar to that of cyclopromazine.

L134, an effective PROTAC BRD4 degrader, exhibits a DC50 value of 7.36 nM. The degradation of BRD4 by L134 is mediated through the ubiquitin-proteasome system in a DCAF11-dependent manner.

PVD-06 is a selective PROTAC-based degrader of PTPN2 (with a selectivity index of greater than 60-fold over PTP1B) and exhibits anticancer activity. It induces the degradation of PTPN2 through ubiquitination and proteasome-dependent pathways. PVD-06 also enhances T cell activation and amplifies IFN-γ-mediated cytotoxicity.

MS33 is a highly effective degrader of the WDR5 protein, exhibiting Kd values of 870 nM and 120 nM for VCB and WDR5, respectively. It induces degradation of WDR5 through an E3 ligase VHL-mediated and proteasome-dependent mechanism. MS33 holds promise for furthering research in the field of acute myeloid leukemia.

YF135, a reversible-covalent KRAS G12C PROTAC, effectively induces the degradation of KRAS G12C and reduces phospho-ERK levels via the E3 ligase VHL-mediated proteasome pathway. Designed by integrating the KRAS G12C inhibitor 48 (compound 6d) as the ligand, YF135 utilizes the MRTX849 linkage VHL ligand scaffold.

SS47, a PROTAC-based HPK1 degrader, induces proteasome-mediated HPK1 degradation and significantly enhances the in vivo antitumor efficacy of BCMA CAR-T cell research. HPK1, an immunosuppressive regulatory kinase, is a promising target for cancer immunotherapies [1].

WBC100 (14-D-Valine-TPL) is a potent, selective, orally active c-Myc glue degrader targeting the ubiquitin E3 ligase CHIP-mediated 26S proteasome pathway, primarily used in research for c-Myc overexpressing tumors [1].

CaMKIIα-PHOTAC is a photochemically targeted chimera (PHOTAC) that specifically targets Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), facilitating its ubiquitination and subsequent proteasome-mediated degradation when exposed to specific light wavelengths. Under illumination, CaMKIIα-PHOTAC diminishes synaptic functions and weakens evoked field excitatory postsynaptic potentials in the mouse hippocampus, impacting physiological responses and sustaining long-term potentiation and memory functions within dendritic domains [1].