protein secretion

IXA4 is a highly selective, nontoxic activator of IRE1/XBP1s and reduces APP secretion by activating IRE1. IXA4-stimulated IRE1 activation also enhanced pancreatic function.

LSN3318839 is a small-molecule compound and a positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), featuring oral activity and selective enhancement of G protein-coupled signaling, which promotes glucose-dependent insulin secretion for blood glucose reduction.

Tirzepatide sodium is the sodium salt form of a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist peptide drug that enhances insulin secretion and improves glycemic control by simultaneously activating GIP and GLP-1 receptors. In research and clinical settings, Tirzepatide sodium has also demonstrated effects in reducing body weight and improving metabolic parameters, and is used in studies related to type 2 diabetes and metabolic disorders.

L-692429 (MK-0751) is a potent nonpeptidyl growth hormone secretagogue (GHS) agonist and benzolactam derivative, known for reversing glucocorticoid-induced inhibition of GH secretion. L-692429 exhibits high affinity for the G protein-coupled receptor and is useful in studying acromegaly and obesity.

LY2881835 is a potent and selective GPR40 agonist.

DSS30 is a P25/CDK5 inhibitor.DSS30 acts by inhibiting the phosphorylation of amyloid precursor protein cleaving enzyme 1 (BACEl), which reduces the secretion of β-amyloid (Aβ).DSS30 can be used for the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease.

LHVS effectively blocks T. gondii microneme protein secretion (IC50=10 μM), gliding motility, and cell invasion. LHVS is a potent, non-selective cysteine protease inhibitor.

RV01 is a novel quinoline-substituted analogue of resveratrol that inhibits DNA damage, reduces ethanol-induced acetaldehyde dehydrogenase (ALDH2) mRNA expression, and has hydroxyl radical scavenging activity. rV01 reduces iNOS expression and has anti-neuroinflammatory effects. rV01 reduces tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion. RV01 reduced tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion, inhibited lps-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, decreased toll-like receptor 4 (TLR4) protein expression, and inhibited lps-induced activation of mitogen-activated protein kinase (MAPK) and nuclear transcription factor-кB (NF-кB) signaling pathways.

RO-28-1675 is a direct and selective glucokinase activator that indirectly affects the activity of the GK/GKRP (glucokinase regulatory protein) complex, with efficacy decreasing with increasing glucose concentration, and can be used in studies related to insulin secretion and type 2 diabetes.

3-Deoxyglucosone(3-Deoxy-D-glucosone) is synthesized by the intermediate pathway of the melad and polyol reactions.3-Deoxyglucosone reacts rapidly with protein amino groups to form advanced glycosylated end proteins (AGEs).3-Deoxyglucosone inactivates glutathione peroxidase and synergizes with low glucose to enhance GLP-1 secretion.3-Deoxyglucosone is used as a biomarker for diabetes mellitus.3-Deoxyglucosone has been shown to be an inhibitor of GLP-1 secretion in the presence of low glucose. 3-Deoxyglucosone inactivates glutathione oxidase, synergizes with low glucose to enhance GLP-1 secretion, and can be used as a biologic marker for diabetes.

STAT3-IN-31 (compound K2071), derived from STATtic, acts as an inhibitor of both STAT3 and mitotic processes. This compound interrupts mitotic progression and impacts the formation of the mitotic spindle. Additionally, STAT3-IN-31 hampers migration in glioblastoma cells, suppresses cellular proliferation within tumor spheroids, induces senescence in glioblastoma, and inhibits the growth of Temozolomide-resistant cells while reducing the secretion of the pro-inflammatory cytokine monocyte chemoattractant protein (MCP-1).

Vasopressin-D5 trifluoroacetate is the trifluoroacetic acid salt form of Vasopressin-D5, an isotopically labeled derivative of Vasopressin. Vasopressin, a cyclic nonapeptide, is synthesized in the medial hypothalamus and plays a critical role in the hypothalamic-pituitary-adrenal axis by enhancing the stimulation of corticotropin-releasing factor, thereby regulating the secretion of adrenocorticotropic hormone. Additionally, Vasopressin acts as a neurotransmitter, exerting its effects through interaction with specific G-protein-coupled receptors.

Ofirnoflastum (Ofirnoflast) is a selective serine/threonine-protein kinase Nek7 inhibitor that exerts potent anti-inflammatory effects by suppressing Nek7-dependent NLRP3 inflammasome activation, reducing caspase-1 cleavage, IL-1β and IL-18 secretion, and pyroptotic cell death in vitro, while significantly attenuating cytokine production and tissue injury in animal models of acute and chronic inflammation, supporting its therapeutic potential in autoimmune and inflammatory diseases.

M351-0056 is an agonist of the immune checkpoint protein VISTA, diminishing cytokine secretion induced by VISTA, enhancing VISTA-induced T cell proliferation, and exhibiting immunomodulatory activity. Additionally, M351-0056 has been shown to improve psoriasis-like dermatitis induced by Imiquimod in mouse models.

Gamma-secretase modulator 6 (Example 50) is a gamma-secretase modulator. It inhibits Aβ42 secretion in HEK cell lines stably expressing APP (Aβ amyloid precursor protein) with a pIC50 of 8.1. This compound is applicable in Alzheimer's disease research.

HPK1-IN-57 (Compound 10c) is an inhibitor of hematopoietic progenitor kinase 1 (HPK1) with an IC50 of 0.09 nM. It suppresses the activity of HPK1 kinase, inhibits the phosphorylation of downstream adaptor protein SLP76 (IC50 of 33.74 nM), and effectively induces the secretion of the T cell activation marker IL-2 (EC50 of 84.24 nM). HPK1-IN-57 holds promise for research in tumor immunotherapy.

HPK1-IN-43 (compound 9f) is an HPK1 kinase inhibitor with an IC50 value of 0.32 nM. It inhibits the phosphorylation of the downstream protein SLP-76 in PBMC cells and enhances the secretion of interleukin 2 (IL-2) and interferon-γ (IFN-γ). HPK1-IN-43 is applicable to cancer research.

GLP-1R modulator-1 (Compound 384) is a potent and orally active selective agonist of the glucagon-like peptide-1 receptor (GLP-1R). It activates G protein-coupled signaling, leading to increased intracellular cAMP levels, enhanced insulin secretion, delayed gastric emptying, and reduced appetite. GLP-1R modulator-1 holds potential for research in type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH).

PDIA1-IN-1 is an inhibitor of protein disulfide isomerase 1 (PDIA1). It effectively hinders the assembly and activity of the NLRP3 inflammasome, with an IC50 value of 1 μM. Additionally, PDIA1-IN-1 can reduce the secretion of IL-1β and is applicable in research related to inflammatory and neurological diseases.

LAB687 (Compound 2a) is an inhibitor of microsomal triglyceride transfer protein (MTP) with an IC50 of 0.9 nM for inhibiting the secretion of apolipoprotein B (apoB) in HepG2 cells. Additionally, LAB687 acts as a Smoothened (Smo) antagonist, exhibiting IC50 values of 2.48 μM and 3.42 μM for mouse and human Smo receptors, respectively. This compound is effective in reducing triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and in inhibiting the Hedgehog signaling pathway.

SMU-R39 is a TLR7 and TLR8 antagonist with IC50 values of 3.22 μM and 0.24 μM, respectively. It binds to recombinant mTLR7 protein (KD= 2.36 μM) and recombinant hTLR8 protein (KD= 105 nM). SMU-R39 inhibits downstream NF-κB and MAPK signaling pathways, reducing the secretion and transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in PBMCs and THP-1 cells. In an Imiquimod (IMQ)-induced psoriasis mouse model, SMU-R39 exhibits anti-inflammatory activity and may be used for researching autoimmune diseases such as psoriasis.

Glycosyltransferase-IN-2 (Compound 20) is an inhibitor of glycosyltransferase with broad-spectrum antiviral activities against coronaviruses. It shows IC50 values of 11.3 μM for MHV, 5.5 μM for HCoV-NL63, and approximately 16.2 μM for SARS-CoV-2. This compound can interfere with coronavirus infectivity, alter viral protein glycosylation, inhibit interaction with the ACE2 receptor, and suppress secretion of cytotoxic viral particles (SC-VLP) and RNA replication. Glycosyltransferase-IN-2 is utilized in coronavirus infection research.

GSTO1-IN-6 is an allosteric covalent inhibitor of GSTO1 with an IC50 of 457 nM. It significantly reduces lipopolysaccharide (LPS)-induced secretion of IL-1β with an IC50 of 1.9 μM and IL-18 with an IC50 of 10 μM in human monocyte-derived macrophages. GSTO1-IN-6 covalently binds to GSTO1-Cys32, inducing conformational changes and protein instability. This compound is applicable in the study of inflammatory diseases.

Lck-IN-5 (example C10) is a potent and selective inhibitor of lymphocyte-specific protein tyrosine kinase (LCK). It specifically disrupts the interaction between the SH3 domain of LCK and the RK motif of CD3ε, inhibiting LCK recruitment to the T-cell receptor. Lck-IN-5 modulates the activity of CD3ε-containing CAR-T and TRuC-T cells, reduces cytokine secretion, and promotes a central memory-like phenotype associated with enhanced persistence. This compound is applicable in research on autoimmune diseases and graft-versus-host disease.