proteasome-mediated

RN-18 antagonizes Vif function and inhibits HIV-1 replication only in the presence of A3G. RN-18 increases cellular A3G levels in a Vif-dependent manner and increases A3G incorporation into virions without inhibiting general proteasome-mediated protein degradation. RN-18 enhances Vif degradation only in the presence of A3G, reduces viral infectivity by increasing A3G incorporation into virions and enhances cytidine deamination of the viral genome.

GS143 is a selective IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. It suppresses NF-κB activation and transcription of target genes without inhibiting proteasome activity. GS143 has anti-asthm[atic] properties.

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

IBR2 (Isoquinoline) is a potent and specific RAD51 inhibitor known for its ability to suppress RAD51-mediated DNA double-strand break repair. By interfering with RAD51 multimerization, accelerating proteasome-mediated RAD51 protein degradation, inhibiting cancer cell growth, and inducing apoptosis, IBR2 has proved to be an effective compound in these aspects.

NSC745885 is an effective down-regulator of EZH2 via proteasome-mediated degradation. NSC745885 is also an effective anti-tumor agent that displays selective toxicity against multiple cancer cell lines but not normal cells. NSC745885 offers possibilities

ERα degrader10 is a potent, selective, orally active estrogen receptor α (ERα) degrader. It demonstrates strong ERα binding affinity (IC50 of 24.0 nM) and degradation capability (EC50 of 5.3 nM). This compound degrades ERα through a proteasome-mediated pathway and is utilized in breast cancer research.

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.

TX2-121-1 targets HER3 for proteasome-mediated degradation to inhibit HER3-dependent signalling and growth.

1. Steviol (NSC-226902), a natural sweetener, it inhibits proliferation of the gastrointestinal cancer cells intensively. 2. Steviol can induce a significant increase in CYP3A29 expression. 3. Steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner. 4. Steviol can treat polycystic kidney disease, it slowed cyst growth, in part, by reducing AQP2 transcription, promoted proteasome, and lysosome-mediated AQP2 degradation.

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.

AQ-101 is a inhibitor of MDM2, which induces MDM2 protein degradation through a self-ubiquitination and proteasome-mediated mechanism.

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].

Anticancer Agent 141 (Compound AE), an antimycin alkaloid, exhibits inhibitory potential against HPV-infected cervical cancer. It impedes HeLa cell proliferation by arresting the cell cycle at the S phase and induces caspase-dependent apoptosis through mitochondrial disruption. This disruption activates the ROS-mediated ubiquitin-dependent proteasome system, leading to the degradation of E6 E7 oncoproteins [1].