proteasome-mediated

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.

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.

NSC745885 is an antitumor agent non-toxic to normal cells that downregulates EZH2 via proteasome-mediated degradation. It exhibits toxicity against multiple normal and drug-resistant cancer cell lines and may be used in studies of advanced bladder cancer and oral squamous cell carcinoma.

VLX 1500 is a potent deubiquitinating enzyme (DUBs) inhibitor designed to overcome resistance to traditional proteasome inhibitors. It triggers ER stress-mediated apoptosis by specifically blocking USP14/UCHL5 activity on the 19S regulatory particle, leading to a lethal accumulation of ubiquitinated proteins, widely used in drug target screening for relapsed hematological malignancies.

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.

NUV-244 is a degrader of PNPLA3 I148M. It reduces the levels of PNPLA3 I148M on lipid droplets through BFAR-mediated ubiquitin-proteasome degradation.

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.

PROTACERK5 degrader-1 (compound 2) is a bifunctional ERK5 PROTAC degrader. It induces the degradation of ERK5 in MOLT-4 cells via a VHL-mediated proteasome pathway. PROTACERK5 degrader-1 is useful for studying diseases or disorders characterized by abnormal ERK5 activity.

CH091138 is a potent and selective KRASG12D PROTAC degrader, exhibiting a DC50 value of 148.3 nM in HeLa cells and 469.8 nM in AsPC-1 cells. It selectively targets both exogenous and endogenous KRASG12D through the VHL-mediated ubiquitin-proteasome system, without affecting KRASWT or other KRAS mutants (G12C/G12S/G12V). CH091138 demonstrates significant antitumor activity by inducing apoptosis (apoptosis) in tumor cells and is applicable for research in pancreatic and colon cancers.

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.

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].

WRR139 is a peptide vinyl sulfone derivative that acts as a potent inhibitor of cytosolic N-glycanase 1 (NGLY1) and the transcription factor Nrf1. NGLY1-mediated deglycosylation is essential for the maturation and activation of Nrf1. By inhibiting NGLY1, WRR139 impairs Nrf1 processing, localization, and activation, thereby suppressing the compensatory expression of proteasome genes. WRR139 significantly potentiates the cytotoxicity of Carfilzomib against cancer cells, serving as a valuable tool for studying proteostasis and overcoming resistance to proteasome inhibitors.

Steviol (Standard) is a reference standard for research and analysis in studies involving Steviol. 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.