misfolding

Icerguastat (IFB-088) is a selective inhibitor of holophosphatase. Sephin1 safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo.

Sephin1 (IFB-088) is reportedly a selective inhibitor of GADD34 (PPP1R15A), which is a stress-induced regulatory subunit of protein phosphatase 1 complex that dephosphorylates eIF2α

IFB-088 acetate, a benzyl guanidine derivative, is used to treat diseases and cancers associated with the PPP1R15A pathway and associated with protein misfolding stress, Examples include tau disease, synaptic riboprotein disease, polyglutamine and polyalanine diseases, leukodystrophy, cystic fibrosis, multiple sclerosis, lysosome storage disorders, amyloidosis diseases, inflammation, metabolic disorders, cardiovascular diseases, osteoporosis, neurological trauma, and more.

CB2R agonist 4 is a cannabinoid receptor 2 (CB2R) agonist with an EC50 value of 6.9 μM. It can induce apoptosis, promote reactive oxygen species (ROS) production, and cause protein misfolding. Additionally, CB2R agonist 4 exhibits cytotoxicity against various tumor cells and is applicable for cancer research.

Cloridarol is an inhibitor of human islet amyloid polypeptide (hIAPP) that prevents its abnormal misfolding and aggregation. It enhances cell viability, inhibits apoptosis, and protects pancreatic β cells from hIAPP-induced cytotoxicity. Cloridarol is applicable in research related to type 2 diabetes (T2D).

NBE5 is an orally active hydrophobic tag-targeted degrader (HyTTD) of Keap1. It mimics protein misfolding to recruit the molecular chaperone Hsp90 and facilitates the targeted degradation of Keap1 through both the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. This process releases the inhibition of the transcription factor Nrf2 by Keap1, thereby powerfully activating Nrf2-mediated endogenous antioxidant pathways and upregulating downstream antioxidant proteins such as HO-1 and GCLM. NBE5 effectively alleviates oxidative stress and inflammatory damage, demonstrating excellent in vivo activity in a DSS-induced acute colitis mouse model.

TAU-IN-6 (Compound 13) is an inhibitor of Tau protein misfolding and aggregation. It prevents the formation of stress granules composed of tau and TIA1, and is utilized in Alzheimer's disease research.

Quinacrine dihydrochloride hydrate possesses antiprotozoal and anti-infective properties and exhibits multi-target biological activity; it inhibits voltage-gated sodium channels (which are involved in the generation and conduction of action potentials) and aldehyde oxidase activity, and acts as a riboflavin antagonist to interfere with riboflavin-related protein interactions; Furthermore, quinacrine has been used in in vitro models to study the regulation of prion misfolding processes.

Fe-TMPyP binds to the prion protein PrP and inhibits misfolding. Fe-TMPyP is also a peroxynitrite decomposition catalyst.

VAS 3947 is a specific inhibitor of NADPH oxidase (NOX).VAS 3947 has a potent anti-platelet effect, inducing apoptosis through UPR activation, mainly due to protein aggregation and misfolding, independent of anti-NOX activity.

CuATSM is a cell-permeable copper complex and PET tracer for selective hypoxia imaging. It also exhibits neuroprotective potential in ALS and Parkinson's disease by mitigating oxidative damage.

NPT200-11 is an orally bioavailable and brain penetrating inhibitor of accumulation of alpha-synuclein (ASYN) misfolding and aggregation. NPT200-11 can be used in studies about the underlying pathology of synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Multiple Systems Atrophy (MSA).

Minzasolmin(DLX-313) is an alpha-synuclein misfolding inhibitor for the study of Parkinson's disease.

CFTRcorrector 14 (Compound SVQ26) functions as a Class 3 corrector targeting the cystic fibrosis transmembrane conductance regulator (CFTR), enhancing CFTR activity (improving activity in the presence of Class 1 corrector VX-809 with an EC50 of 3.08 μM). It addresses the misfolding and functional impairments of CFTR proteins caused by mutations. CFTRcorrector 14 is used in cystic fibrosis research.

Oncocin is an antibacterial peptide classified under proline-rich antimicrobial peptides (PrAMPs). It is effective against Gram-negative bacteria, exhibiting a minimum inhibitory concentration (MIC) range of 0.125-8 μg/mL for 34 clinical isolates and strains of Enterobacteriaceae and non-fermentative bacteria. Oncocin interacts with the substrate-binding domain of the chaperone protein DnaK, with a dissociation constant in the micromolar range. This interaction results in protein misfolding and aggregation, ultimately causing bacterial cell death.