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).

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].