ubiquitinated

Proteasome inhibitor IX (PS-IX) is an inhibitor of chymotrypsin-like activity of the 20S proteasome (IC50 ~1 μM). Proteasome inhibitor IX shows potent anticancer activity. Proteasome inhibitor IX exhibits HCT116 p53+/+ cells growth inhibitory activity(IC50 = 1.49 μM).

M3258 is an immunoproteasome subunit LMP7 (β5i) inhibitor, with an IC50 of 3.6 nM for LMP7 and 3.4 nM at the cellular level. In a multiple myeloma xenograft model, M3258 exhibits significant antitumor activity. In multiple myeloma cells, M3258 significantly and persistently inhibits LMP7 activity and ubiquitinated protein turnover in tumor tissues, further inducing apoptosis.

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.

BIO-2007817 is a positive allosteric modulator (PAM) of Parkin, an E3 ubiquitin ligase. This compound enhances the activity of wild-type Parkin, stimulates Parkin's autoubiquitination, and induces the appearance of mono-ubiquitinated forms of Miro1 (a Parkin substrate) with an EC50 of 0.17 μM.

TCL1 acts as a selective non-covalent inhibitor targeting the Pru domain of the Rpn-13 subunit within the 19S regulatory particle (19S RP) of the proteasome, with an IC50 value around 26 μM. It disrupts the recognition and transport of ubiquitinated proteins by Rpn-13, thus inhibiting proteasomal degradation and affecting intracellular protein metabolism balance. TCL1 holds potential for research in hematologic malignancies.

DDO-7263 is a 1,2,4-Oxadiazole derivative that upregulates Nrf2 through binding to Rpn6 to block the assembly of 26S proteasome and the subsequent degradation of ubiquitinated Nrf2. DDO-7263 is a potent Nrf2 activator that activates the Nrf2-ARE signaling pathway and exerts anti-inflammatory activity [1].

Prostaglandin J2 (PGJ2), a derivative of Prostaglandin D2 (PGD2), serves as a potent agonist for PGD2 receptors (DP), exhibiting affinity constants (K i) of 0.9 nM and 6.6 nM for hDP and hCRTH2 receptors, respectively. It activates cyclic AMP production with an EC50 of 1.2 nM, induces oxidative stress, neuronal apoptosis, and promotes the accumulation of ubiquitinated (Ub) proteins. Notably, PGJ2's neurotoxic properties are implicated in the progression of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD) [1] [2] [3] [4].

CNB-001 is a potent inhibitor of 5-lipoxygenase (5-LOX) that reduces 5-LOX expression while enhancing proteasome activity. It also increases phosphorylation of eIF2α and levels of HSP90 and ATF4 in Alzheimer's disease transgenic mice, thereby limiting soluble Aβ and ubiquitinated aggregated protein accumulation. Additionally, CNB-001 maintains synapse-associated protein expression and improves memory, making it a valuable compound for Alzheimer's disease research [1].

TNG348 is an allosteric, selective, and reversible inhibitor of USP1, causing dose-dependent accumulation of ubiquitinated substrates in vitro and in vivo. CRISPR screens demonstrate that TNG348 disrupts DNA damage tolerance by interfering with the translesion synthesis pathway via RAD18-dependent ubiquitinated PCNA. Although both TNG348 and PARP inhibitors selectively kill homologous recombination-deficient tumors, they act through distinct mechanisms: PARP1 knockout confers resistance to PARP inhibitors but sensitizes cells to TNG348. Consistent with this mechanistic divergence, combining TNG348 with PARP inhibitors results in synergistic antitumor efficacy, including tumor growth inhibition and regression in multiple HRD mouse xenograft models.

Prostaglandin J2 (Standard) is a reference standard for research and analysis in studies involving Prostaglandin J2. Prostaglandin J2 (PGJ2), a derivative of Prostaglandin D2 (PGD2), serves as a potent agonist for PGD2 receptors (DP), exhibiting affinity constants (K i) of 0.9 nM and 6.6 nM for hDP and hCRTH2 receptors, respectively. It activates cyclic AMP production with an EC50 of 1.2 nM, induces oxidative stress, neuronal apoptosis, and promotes the accumulation of ubiquitinated (Ub) proteins. Notably, PGJ2's neurotoxic properties are implicated in the progression of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD) [1] [2] [3] [4].