protein homeostasis

Corrector C4, a corrector commonly used to study cystic fibrosis mutants, works by alleviating the interaction between CFTR transmembrane domain mutants and protein homeostasis.

Rosolutamide (ALZ-003) is a curcumin analog, an orally active Nrf1 and Nrf2 activator.Rosolutamide modulates oxidative homeostasis, improves mitochondrial function and promotes autophagy, reduces mutant protein aggregation, and decreases intracellular mitochondrial reactive oxygen species (ROS) levels.Rosolutamide has been used in the study of neurodegeneration such as spinal cerebellar ataxia and Huntington disease. neurodegenerative diseases such as Huntington's disease. Regulates oxidative homeostasis.

BRD5631 is an autophagy enhancer that operates through an mTOR-independent pathway. It influences several cellular disease phenotypes associated with autophagy, such as protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in cellular homeostasis and disease. [1].

GSK256073 is an orally active GPR109A agonist. GSK256073 also is a long-lasting and non-flushing HCA2 (hydroxy-carboxylic acid receptor 2) full agonist (pEC50: 7.5). GSK256073 acutely improves glucose homeostasis via inhibition of lipolysis.

ALT-007 is an orally bioavailable inhibitor of serine palmitoyltransferase (SPT), the rate-limiting enzyme in de novo ceramide synthesis. In murine models of age-related sarcopenia, ALT-007 effectively restores muscle mass and function impaired by aging. Additionally, ALT-007 may enhance protein homeostasis in Caenorhabditis elegans and in mouse models of aging and age-associated diseases, acting as a ceramide inhibitor.

AA-BR-157 is a PROTAC degrader targeting metallothionein 2A (MT2A) with a DC50 of 190 nM. It downregulates DIAPH3, a protein involved in cytoskeletal and cellular movement regulation, inhibiting cell migration in MDA-MB-231 and U-87 MG cell lines. Additionally, AA-BR-157 modulates zinc homeostasis in MDA-MB-231 cells. (Pink: ligand for target protein MT2A ligand 1; Black: linker; Blue: ligand for VHL E3 ligase).

BRI-50460 is an inhibitor of cytosolic calcium-dependent phospholipase A2 (cPLA2) with the ability to cross the blood-brain barrier, exhibiting an IC50 of 0.88 nM. By inhibiting cPLA2, BRI-50460 modulates downstream inflammatory lipid signaling pathways, mitigating the effects of amyloid β42 oligomers on cPLA2 activation, tau protein hyperphosphorylation, and synaptic and dendritic loss. This results in its activity in regulating neuroinflammation and restoring lipid homeostasis. BRI-50460 is applicable in research related to Alzheimer's disease and other neurodegenerative disorders.

HDAC6-IN-60 (Compound 12) is an orally active, selective inhibitor of HDAC6. By inhibiting the enzymatic activity of HDAC6 and modulating pathways related to protein homeostasis, HDAC6-IN-60 affects the proliferation of tumor cells. It holds potential for research in HDAC6-related cancers.

Neuromedin U-23 (NMU-23) is a neuropeptide involved in diverse biological processes, including smooth muscle contraction, energy homeostasis, and nociception.1It is an agonist of neuromedin-U receptor 1 (NMUR1; EC50= 0.17 nM for the human receptor in a calcium mobilization assay using HEK293 cells) and NMUR2 (EC50= ~1.4-2 nM for arachidonic acid release in CHO cells expressing the human receptor).2,3NMU-23 (1 μM) induces contractions in isolated rat colon smooth muscle strips.4It decreases body weight and food intake and increases core body temperature in mice when administered at a dose of 36 μg/animal.5Intrathecal administration of NMU-23 decreases the mechanical pain threshold in the von Frey test in rats.6 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBr. J. Pharmacol.158(1)87-103(2009) 2.Szekeres, P.G., Muir, A.I., Spinage, L.D., et al.Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3J. Biol. Chem.275(27)20247-20250(2000) 3.Hosoya, M., Moriya, T., Kawamata, Y., et al.Identification and functional characterization of a novel subtype of neuromedin U receptorJ. Biol. Chem.275(38)29528-29532(2000) 4.Brighton, P.J., Wise, A., Dass, N.B., et al.Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissueJ. Pharmacol. Exp. Ther.325(1)154-164(2008) 5.Peier, A., Kosinski, J., Cox-York, K., et al.The antiobesity effects of centrally administered neuromedin U and neuromedin S are mediated predominantly by the neuromedin U receptor 2 (NMUR2)Endocrinology150(7)3101-3109(2009) 6.Yu, X.H., Cao, C.Q., Mennicken, F., et al.Pro-nociceptive effects of neuromedin U in ratNeuroscience120(2)467-474(2003)

CAY10722 is an inhibitor of sirtuin 3 (SIRT3), a class III HDAC (71% inhibition at 200 μM). SIRT3 is involved in modulating metabolic homeostasis as a NAD+-dependent protein deacetylase in the mitochondria. SIRT3 functions as either an oncogene or tumor suppressor, depending on cancer cell type. High SIRT3 expression in patient-derived esophageal cancer tissues is associated with shorter survival and, in mice, downregulation leads to a lower tumor load. In contrast, low SIRT3 expression in patient-derived breast cancer cells is correlated with shorter survival.

VCP p97 inhibitor-1, a highly effective compound, inhibits VCP p97 (also known as Cdc48, CDC-48, or Ter94) with an IC 50 of 54.7 nM. This inhibitor induces a disruption in protein homeostasis and interferes with the degradation process of misfolded polypeptides by the ubiquitin-proteasome system (UPS).

GUANOSINE 3':5'-CYCLIC MONOPHOSPHATE SOD (cGMP sodium salt) , also known as cGMP, is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin. GUANOSINE 3':5'-CYCLIC MONOPHOSPHATE SOD activates protein kinase G (PKG) and modulates ion channel conductance, with signaling affecting diverse processes including smooth muscle relaxation and proliferation, phototransduction, and energy homeostasis.

BOLD-100 free base (NKP-1339; IT-139), a ruthenium-based anticancer agent, inhibits stress-induced GRP78 upregulation, thus disrupting endoplasmic reticulum (ER) homeostasis. This action induces ER stress and unfolded protein response (UPR), interfering with the intricate relationship between ER-stress response, lysosome dynamics, and autophagy execution.

Hepcidin-1 (mouse) TFA, an endogenous peptide hormone, regulates iron homeostasis by upregulating mRNA levels of TRAP, cathepsin K, and MMP-9, enhancing TRAP-5b protein secretion, and downregulating FPN1 protein levels, thereby increasing intracellular iron. It also promotes osteoclast differentiation [1].

Peresolimab is a humanized immunoglobulin G1 kappa (IgG1-κ) monoclonal antibody designed to target the programmed cell death protein 1 (PD-1) receptor, and it potentially functions by stimulating physiological immune inhibitory pathways to restore immune homeostasis and maintain self-tolerance, which can be applied in the research of autoimmune conditions such as rheumatoid arthritis.

EB-3D is a potent and selective choline kinase alpha 1 (ChoKα1) inhibitor (IC50: 1 μM) with anti-cancer activity.

SPC-180002, a dual SIRT1 3 inhibitor, exhibits IC50 values of 1.13 and 5.41 μM for SIRT1 and SIRT3, respectively. It disrupts redox homeostasis through ROS generation, consequently enhancing p21 protein stability and inducing mitochondrial dysfunction. Furthermore, this compound significantly impedes cell cycle progression and malignancy proliferation, while also activating the Nrf2 signaling pathway [1].

VE-PTP-IN-1 (compound 2) is a selective inhibitor of vascular endothelial protein tyrosine phosphatase (VE-PTP) with weakly acidic properties, and it plays a role in regulating vascular homeostasis and angiogenesis.

Neuromedin S (human), a 33-amino acid neuropeptide, serves as an endogenous ligand for the orphan G-protein coupled receptor (GPCR) FM-4 TGR-1, and acts on the neuromedin U (NMU) receptor 2 (NMUR2) to regulate body weight homeostasis [1].

REM127 is a small molecular compound that modulates cellular calcium homeostasis and provides neuroprotection. It efficiently restores the imbalance of calcium homeostasis in cell models caused by the pathological accumulation of tau protein. Furthermore, REM127 can effectively cross the blood-brain barrier and offers therapeutic benefits in animal models of Alzheimer's disease, particularly in ameliorating synaptic and cognitive deficits and slowing the progression of amyloid-beta and tau pathologies. This compound is utilized in the research of neurodegenerative diseases.

Recombinant Humanized Type XVII Collagen is a transmembrane protein that forms hemidesmosomes. It facilitates interactions between stem cells, surrounding cells, and the extracellular matrix, thereby regulating skin homeostasis, aging, and wound healing. Additionally, Recombinant Humanized Type XVII Collagen has distinct cell adhesion sites and signal transduction capabilities, which can modulate cell migration, proliferation, and differentiation.