oligomerization

IRE1α kinase-IN-1 is a highly selective IRE1α (ERN1) inhibitor, with an IC50 of 77 nM, displaying 100-fold selectivity over the IRE1β isoform. It inhibits ER stress-induced IRE1α oligomerization and autophosphorylation, as well as IRE1α RNase activity (IC50=80 nM).

VBIT-4 is a voltage-dependent anion channel 1 (VDAC1) oligomerization inhibitor (Kd: 17 μM). VBIT-4 can be used for therapeutic purposes in apoptosis-associated disorders (such as neurodegenerative and cardiovascular diseases).

NLRP3/AIM2-IN-3 is a unique molecule that inhibits NLRP3 and AIM2 inflammasome activation in a species-specific manner. It has an IC50 value for cell lysis of 0.077 ± 0.008 μ M. NLRP3/AIM2-IN-3 is a potent inhibitor of NLRP3 and AIM2 inflammasome-dependent cell lysis with an IC50 value for cell lysis of 0.077 ± 0.008 μ M. NLRP3/AIM2-IN-3 inhibits LPS/nigericin NLRP3/AIM2-IN-3 inhibits LPS/nigericin-stimulated cell lysis in THP-1 macrophages with an IC50 value of 0.077 ± 0.008 μM. NLRP3/AIM2-IN-3 interferes with the interaction of NLRP3 or AIM2 with the bridging protein ASC, inhibiting oligomerization of ASC.

G6PD activator AG1 is a glucose-6-phosphate dehydrogenase (G6PD) agonist that promotes glucose-6-phosphate dehydrogenase (G6PD) oligomerization to a catalytically competent form. G6PD activator AG1 reduces oxidative stress in cells and zebrafish, reduces chloroquine or diamide-induced oxidative stress in human erythrocytes, and can be used to study glucose-6-phosphate dehydrogenase deficiency.

Bis-T-23 is a promoter of actin-dependent dynamin oligomerization, an HIV-I integrase inhibitor, and a Telstar derivative. Bis-T-23 promotes actin-dependent dynamin oligomerization. Bis-T-23 can be used in studies of HIV and chronic kidney disease (CKD).

3,6-DMAD dihydrochloride is an acridine derivative and a potent inhibitor of the IRE1α-XBP1s pathway. 3,6-DMAD dihydrochloride can induce IL-6 secretion by exploiting the IRE1α-XBP1s pathway. 3,6-DMAD dihydrochloride is a potent inhibitor of the IRE1α-XBP1s pathway. 3,6-DMAD dihydrochloride has inhibitory effects on IRE1α oligomerization and RNase activity. 3,6-DMAD dihydrochloride can be used in cancer research.

NOD1/2 antagonist-1 is a dual inhibitor of nucleotide-binding oligomerization domain-like receptors NOD1 and NOD2, exhibiting IC50 values of 1.13 uM for NOD1 and 0.77 uM for NOD2, with an acceptable half-life of 67.6 minutes. NOD1/2 antagonist-1 enhances the antitumor efficacy of paclitaxel and serves as a potent experimental tool for investigating innate immune receptor-mediated signaling and cancer therapy modulation.

Entacapone sodium salt inhibits catechol-O-methyltransferase(COMT) with similar IC50 in different tissues including live, duodenum, kidney and lung, but entacapone is more active than tolcapone in those tissues. Entacapone (< 100 μM) is a potent inhibitor of α-syn and β-amyloid (Aβ) oligomerization and fibrillogenesis, and also protects against extracellular toxicity induced by the aggregation of both proteins in PC12 cells.Entacapone sodium salt is a specific, potent, peripherally acting catechol-O-methyltransferase (COMT) inhibitor with IC50 of 151 nM for PD treatment.

VBIT-3 is a voltage-dependent anion channel 1 (VDAC1) oligomerization inhibitor (Kd: 31.3 μM). VBIT-3 also is an apoptosis inhibitor, can be used for therapeutic purposes in apoptosis-associated disorders (such as neurodegenerative and cardiovascular diseases).

AKOS-22 is a potent mitochondrial protein VDAC1 (voltage-dependent anion channel 1) inhibitor (Kd=15.4 μM). AKOS-22 protects against mitochondrial dysfunction[1]. AKOS-22 interacts with VDAC1 and inhibiting both VDAC1 oligomerization and apoptosis.

CBR-5884 is an selective, active of phosphoglycerate dehydrogenase (PHGDH) inhibitor with an IC50 of 33 μM. CBR-5884 inhibits de novo serine synthesis in cancer cells and is selectively toxic to cancer cell lines with high serine biosynthetic activity. CBR-5884 selectively inhibits the proliferation of melanoma and breast cancer lines that have a high propensity for serine synthesis. Biochemical characterization of the inhibitor revealed that it was a noncompetitive inhibitor that showed a time-dependent onset of inhibition and disrupted the oligomerization state of PHGDH

MSN-125 effectively inhibits Bax/Bak-mediated apoptosis in HCT-116, BMK Cells, and primary cortical neurons protect primary neurons against glutamate excitotoxicity. MSN-125 is an effective Bax and Bak oligomerization inhibitor. MSN-125 prevents mitochond

TC13172 is a potent and covalent inhibitor that specifically targets the mixed lineage kinase domain-like protein (MLKL), exhibiting significant selectivity for MLKL over the closely related receptor-interacting serine/threonine kinase 1 (RIPK1) and RIPK3 at a concentration of 10 µM.TC13172 effectively inhibits necroptosis induced by the TSZ combination (TNF-α, a Smac mimetic, and Z-VAD-FMK) in HT-29 cells with a EC50 of 2 nM and, at 100 nM, blocks TSZ-induced oligomerization and plasma membrane translocation of MLKL.

CBI1 formic is a covalent inhibitor of BAX, selectively derivatizing BAX at C126 and inhibiting its activation by triggering with a ligand or point mutation. This compound effectively blocks the t-2-hex lipidation and oligomerization of BAX. Additionally, CBI1 formic inhibits BAX activation induced by BH3 ligands, F116A mutations, or t-2-hex.

TLR7 agonist27 (compound 24) is an effective TLR7 agonist with an EC50 of 238.1 nM. It exhibits weak agonistic activity towards NOD2 (nucleotide-binding oligomerization domain 2) with an EC50 of 6.2 μM. TLR7 agonist27 serves as a potent immunostimulant and can be utilized as a vaccine adjuvant and/or an immunotherapeutic agent.

Tau-0N4R-IN-1 (Compound 6T) is a brain-penetrant inhibitor of tau0N4R oligomerization. It effectively inhibits the fibrillization of tau 0N4R, 2N3R, and 2N4R, showcasing potent anti-seeding effects against tau in vitro, and can dose-dependently reduce α-syn oligomerization while preventing the formation of α-syn inclusions. Tau-0N4R-IN-1 demonstrates stability in mouse microsomes and reduces Aβ plaques derived from the brain tissue of AD patients. Moreover, it exhibits favorable pharmacokinetic properties in mice.

tau Protein/α-synuclein-IN-2 (Compound 14T) is a tau and α-synuclein inhibitor capable of crossing the blood-brain barrier. It reduces α-synuclein oligomerization in a dose-dependent manner through a thiourea linker structure. In biosensor cells, tau Protein/α-synuclein-IN-2 prevents tau aggregation seed effects. In the M17D neuroblastoma model, this compound exhibits anti-inclusion effects and reduces Aβ plaque formation. tau Protein/α-synuclein-IN-2 shows potential for Alzheimer's and Parkinson's disease research.

FK-565 is a ligand of nucleotide-binding oligomerization domain-1 (NOD1) that induces a mouse model of arteritis.

PBA-1105 TFA is an autophagy-targeting chimera (AUTOTAC) that induces p62 self-oligomerization. This compound selectively binds to the exposed hydrophobic regions of misfolded proteins, promoting their degradation through the autophagy (autophagy) pathway. Additionally, PBA-1105 TFA enhances the autophagic flux of Ub-bound aggregates.

NLRP3-IN-70 (Compound 5m) is an inhibitor of the NLRP3 inflammasome with low oral bioavailability. It binds directly to the NACHT domain of the NLRP3 protein, thereby blocking its interaction with ASC, which inhibits ASC oligomerization and the assembly of the NLRP3 inflammasome. NLRP3-IN-70 is applicable in studies on sepsis and non-alcoholic steatohepatitis.

2N4R Tau/α-Syn against-1 (Compound 4d) targets α-synuclein and tau proteins, inhibiting the fibrillization and oligomerization of these proteins, and displays depolymerization activity against Aβ fibers. 2N4R Tau/α-Syn against-1 is applicable in Parkinson's and Alzheimer's disease research.

NLRP3-IN-78 (compound 21) is an NLRP3 inhibitor with a 46.72% inhibition rate of GSDMD-induced pyroptosis at 5 μM. It binds to the NLRP3 protein and prevents GSDMD-NT oligomerization. Additionally, NLRP3-IN-78 inhibits GSDMD cleavage and upstream NF-κB signaling, demonstrating anti-inflammatory activity.

CSC-6 is an inhibitor of NLRP3. It significantly reduces the secretion of IL-1β in PMATHP-1 cells, with an IC50 of 2.3 μM. CSC-6 specifically binds to NLRP3 and prevents its activation by obstructing ASC oligomerization during the NLRP3 assembly process. It effectively alleviates symptoms of sepsis and gout mediated by excessive NLRP3 activation in mouse models.

CBI1 is a covalent BAX inhibitor. It selectively derivatizes BAX at C126 and inhibits BAX activation by triggering a ligand or through point mutations. CBI1 prevents the lipidation and oligomerization of BAX by t-2-hex. It also inhibits BAX activation induced by BH3 ligands, F116A mutation, or t-2-hex.