Immunology and Inflammation

<p>2-Guanidinobenzimidazole (2GBI) is a selective agonist of NLRP3, with a KD value of 1.29 μM for His-GFP-NLRP3. It directly binds to the LRR domain of NLRP3, facilitating the assembly and activation of the inflammasome. Additionally, 2-Guanidinobenzimidazole enhances antitumor immunity, inhibits tumor growth, and overcomes resistance to immune checkpoint blockade (ICB).</p>

<p>IRAK4-IN-11 (compound 6) is a potent inhibitor of IRAK4 with an IC 50 of 0.008 μM. IRAK4-IN-11 exhibits cell pIRAK4 potencies with an IC 50 of 0.19 μM [1].</p>

<p>E5090 is a novel orally active inhibitor of IL-1 generation. It also has anti-inflammatory properties.</p>

<p>COX-2/PI3K-IN-2 (5f): anti-inflammatory &amp; anti-cancer, selectively inhibits COX-2 (Ki=3.02nM), potently blocks PI3K (IC50=2.78nM).</p>

<p>VISTA-IN-3 (Compound A4), a potent small molecule inhibitor of VISTA, exhibits a dissociation constant (K D) of 0.49 μM. This compound effectively induces the release of IFN-γ cytokines and demonstrates synergistic enhancement of anti-cancer activity when combined with PD-L1 antibody [1].</p>

<p>AMS-17, a strong NLRP3 inhibitor, quells microglia activation and cytokines like caspase-1, TNF-α, IL-1β, iNOS in studies.</p>

<p>IL-17 modulator 5 is a IL-17 inhibitor, with an IC 50 of 1 nM .</p>

<p>NLRP3-IN-29 (Compound 5M) is an inhibitor of NLR family pyrin domain containing 3 (NLRP3) with potential for blood-brain barrier permeability and inflammation inhibition both in vivo and in vitro. It can be used for research on Alzheimer's disease [1].</p>

<p>(S,R,S)-AHPC-Boc derivative 1 (Compound 80-9; VH032-Boc derivative 1) is a selective proteasomal degrader targeting MALT1, which recruits the E3 ubiquitin ligase CRBN to form a ternary complex with MALT1. This interaction leads to the ubiquitination and subsequent proteasomal degradation of MALT1. By disrupting the CBM complex, (S,R,S)-AHPC-Boc derivative 1 inhibits the NF-κB signaling pathway and shows potential in inducing apoptosis in ABC-DLBCL cells. It holds promise for research into MALT1-dependent cancers, such as diffuse large B-cell lymphoma (DLBCL).</p>

<p>COX-2-IN-8 (Compound 6a) is a potent, selective, orally active COX-2 inhibitor (IC50: 6.585 μM) with a higher COX-2 selectivity than Celecoxib.</p>

<p>SP11 is a mitochondrial reactive oxygen species (ROS) inhibitor. It activates Fis1 with an IC50 of 9.4 µM by binding to Cys41 and enhances the translocation of Drp1 to mitochondria. SP11 is utilized for research into oxidative stress damage.</p>

<p>Galectin-8-IN-1 selectively binds galectin-8N with 48 μM affinity, 15x more than galectin-3.</p>

<p>Amilo-5MER (5-MP) is an orally active and selective inhibitor of serum amyloid A (SAA). It specifically suppresses the release of pro-inflammatory cytokines IL-6 and IL-1β in SAA-activated cells. Amilo-5MER reduces chronic inflammation and alleviates symptoms of diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). It holds potential for research in autoimmune and chronic inflammatory diseases.</p>

<p>Compound O15, an Osthole derivative, is a potent Nrf2 agonist with an EC50 of 2.9 μM; it inhibits Keap1-Nrf2 binding and Nrf2 ubiquitination.</p>

<p>cGAS-IN-2 (compound 109) serves as a potent inhibitor of Cyclic GMP-AMP Synthase (cGAS), exhibiting an IC50 of 0.01512 μM against h-cGAS [1].</p>

<p>Cryptopleurine is an inhibitor of gene products associated with cell proliferation, survival, invasion and angiogenesis. It acts by targeting the NF-κB pathway.</p>

<p>BIO-8169, a selective interleukin receptor-associated kinase 4 (IRAK 4) inhibitor, demonstrates potent activity with an IC 50 value of 0.23 nM. Exhibiting strong pharmacokinetic properties, BIO-8169 effectively reduces pro-inflammatory cytokine production and mitigates autoimmune encephalomyelitis in the EAE mouse model. Additionally, it has notable blood-brain penetration, evidenced by a rat Kpu,u of 0.7.</p>

<p>CD73-IN-12, a compound from CN114437038A, shows strong anti-tumor activity by effectively inhibiting CD73 enzyme.</p>

<p>TLR4/JNK/NF-κB-IN-1 (Racemic-11k) is an inhibitor of TLR4, JNK, and NF-κB. It suppresses NO production in LPS-stimulated RAW264.7 cells with an IC50 of 23.2 µM. By inhibiting TLR4 expression and reducing JNK phosphorylation, TLR4/JNK/NF-κB-IN-1 prevents NF-κB activation. This leads to a decrease in the transcription of inflammation-related genes, reducing the expression of iNOS and COX-2, and the production of inflammatory mediators such as NO, PGE2, and TNF-α, thereby exhibiting anti-inflammatory activity. TLR4/JNK/NF-κB-IN-1 holds potential in the study of inflammatory diseases, including rheumatoid arthritis and various other inflammatory conditions.</p>

<p>GB1490 is an orally administered galectin inhibitor, demonstrating Kd values of 0.4 μM for galectin-1 and 2.7 μM for galectin-3 [1].</p>

<p>IRAK4-IN-30 (Compound I) is an inhibitor of IRAK4, with an IC50 of 0.6 nM.</p>

<p>Methoxyurea (Compound 3) is a potential modulator of nitric oxide (NO) donors, interacting with hemoglobin forms such as oxyhemoglobin (OxyHb) and methemoglobin (MetHb). It holds promise for use in research on sickle cell disease (SCD).</p>

<p>S-MTC acetate (S-Methyl-L-thiocitrulline acetate) serves as a potent inhibitor of inducible nitric oxide synthases and is especially effective in inhibiting the constitutive (neuronal) type rather than the inducible (endothelial) type.</p>

<p>meso-Zeaxanthin accumulates in the central retina and, together with lutein and zeaxanthin, forms the macular pigment, which functions as a light filter. meso-Zeaxanthin can quench reactive oxygen species (ROS), thereby exhibiting antioxidant properties.</p>

<p>TLR7/8 agonist 7 activates immune cells, useful in ISAC synthesis and immunity research.</p>

<p>mPGES1-IN-4 (compound 32) is a multi-substituted pyrimidine compound acting as a submicromolar inhibitor of PGE2 production. It primarily exerts its anti-inflammatory effects by inhibiting mPGES-1 and significantly suppresses acute inflammation models in vivo.</p>

<p>NLRP3-IN-53 (compound 1) is an NLRP3 inhibitor with an IC50 of 3.4nM.</p>

<p>VS-15 is a selective inhibitor of IDO1, specifically binding to its apo-heme form. Additionally, VS-15 serves as an inhibitor of iNOS.</p>

<p>CB-1158 is a potent and orally bioavailable inhibitor of arginase (IC50s: 86 and 296 nM for recombinant human arginase 1 and 2).</p>

<p>COX-2/NO-IN-1: oral iNOS &amp; NO blocker (IC50=3.52μM), COX-2 supressor, anti-inflammatory, protects kidneys.</p>

<p>(R)-cGAS-IN-4 (Compound 77A*) is the R-enantiomer of cGAS-IN-4, which acts as an orally active inhibitor of cyclic GMP-AMP synthase-adenosine synthase (cGAS).</p>

<p>Trans-3-(3-Pyridyl)acrylic acid (compound 15) is a trans-3-aryl acrylic acid demonstrating antiviral activity against tobacco mosaic virus (TMV) [1].</p>

<p>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.</p>

<p>TMV-IN-8 (compound 7d) is an anti-tobacco mosaic virus (TMV) agent with an antiviral EC50 of 157.6 μg/mL. TMV-IN-8 blocks the assembly of TMV by binding with coat protein (Kd = 0.7 μM) and suppresses TMV coat protein gene expression and biosynthesis process [1].</p>

<p>TLR7 agonist28 (compound 3) is a potent TLR7 agonist. This compound can be combined with anti-tumor monoclonal antibodies (mAb) for use in cancer immunotherapy.</p>

<p>(R)-Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) that exhibits oral activity and analgesic properties. Unlike its counterpart, (R)-Ketoprofen does not significantly enhance the increase of inflammatory cytokines (such as Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1)) induced by LPS. However, it can inhibit the anti-inflammatory activity of (S)-Ketoprofen.</p>

<p>DBMB is a spleen tyrosine kinase (Syk) inhibitor that significantly suppresses Syk enzyme activity. It possesses anti-inflammatory properties by inhibiting NF-κB signaling, thereby reducing the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2). DBMB can be utilized in research on inflammatory diseases.</p>

<p>6,2′,4′-Trimethoxyflavone is an AhR antagonist that does not demonstrate effective protection against ischemia-reperfusion injury in the brain of Sprague-Dawley rats.</p>

<p>iNOs-IN-1 (YPW) is a strong iNOS inhibitor with dose-dependent anti-inflammatory properties, reducing IL-6, iNOS, and NO levels.</p>

<p>AhR agonist 2 is aryl hydrocarbon receptor (AhR) agonist,oral, inducing rapid nuclear enrichment of the AhR and facilitating skin barrier repair,psoriasis.</p>

<p>Factor B-IN-3 is a potent inhibitor of complement factor B. Factor B-IN-3 can be used to study inflammatory and immune-related diseases.</p>

<p>ND-2158 is a potent and selective inhibitor of IRAK4.</p>

<p>MPGES-1, potential anti-inflammatory drug target, has IC50 of 0.03 μM with mPGES-1-IN-1.</p>

<p>nNOS-IN-5 (Compound 9) is a potent inhibitor of human neuronal nitric oxide synthase (nNOS) with a Ki of 22 nM. It exhibits remarkable selectivity, being 900 times more selective for human nNOS over endothelial nitric oxide synthase (eNOS). nNOS-IN-5 is applicable in research related to neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.</p>

<p>NOD1/2 antagonist-1 inhibits NOD1 (IC50 1.13 μM) and NOD2 (IC50 0.77 μM), enhances paclitaxel antitumor efficacy and is used to study innate immune signaling.</p>

<p>HPK1-IN-56 (Compound A29) is an HPK1 inhibitor with an IC50 of 2.70 nM. It inhibits downstream p-SLP76 in Jurkat T cells with an IC50 of 8.1 nM. Additionally, HPK1-IN-56 induces IL-2 production in human PBMCs. This compound exhibits anticancer properties, enhancing T cell cytotoxicity and the antitumor efficacy of anti-PD-1 antibodies.</p>

<p>iNOS/PGE2-IN-1: iNOS/PGE2 inhibitor, reduces LPS-induced NO, low ulcer risk, anti-inflammatory.</p>

<p>Rafutrombopag is a thrombopoietin (TPO) agonist.</p>

<p>GNE-2256, also known as molecule 19, is an orally active compound that inhibits Interleukin 1 receptor-associated kinase 4 (IRAK4) with a K i of 1.4 nM and has</p>

<p>CDA-IN-3 (NCDI) is a chitin deacetylase (CDA) inhibitor with antiparasitic properties. It disrupts chitin metabolism in nematodes, increasing ROS levels within these organisms and causing cellular damage. CDA-IN-3 significantly inhibits all developmental stages of Caenorhabditis elegans and can be utilized in research focused on anti-infective applications.</p>

<p>ASP8731 is a selective inhibitor of BACH1 that prevents inflammation and vascular occlusion, and induces fetal hemoglobin in sickle cell disease.</p>

<p>ARG1-IN-1 is a human arginase 1 inhibitor with an IC 50 of 29 nM.</p>

<p>CD73-IN-2 is a potent inhibitor of CD73 (IC50: 0.09 nM).</p>

<p>NLRP3/AIM2-IN-1 is an inhibitor of thermal sepsis (IC50 = 3.136 ± 0.7667 μM).</p>

<p>Galectin-3-IN-6 (Compound 12) is an orally active galectin-3 (Gal-3) inhibitor, with an IC50 of 12 nM and a Kd of 13 nM for Gal-3. In a CCl4-induced mouse model of acute liver injury and fibrosis, Galectin-3-IN-6 significantly reduces fibrosis markers collagen-1 and α-smooth muscle actin (αSMA) by 64% and 71%, respectively, demonstrating notable anti-fibrotic activity. Galectin-3-IN-6 is applicable for research in fibrosis-related diseases, cancer, and cardiovascular disorders.</p>

<p>SDH-IN-25 is an SDH inhibitor with an IC50 of 4.82 mg/L, demonstrating broad-spectrum and potent antifungal activity. By binding to SDH amino acid residues (TRP173, TYR58, and ARG43), it mimics the action mode of the commercial fungicide flutolanil. SDH-IN-25 induces changes in hyphal morphology, disrupts respiratory metabolism by binding to complex II, generates reactive oxygen species (ROS), and affects mitochondrial membrane potential (MMP) in hyphae. This compound is utilized in agricultural disease control research.</p>

<p>NOS-IN-2: potent, selective imidamide NOS inhibitor, IC50=20μM for iNOS, spares eNOS, low toxicity, useful in inflammation research.</p>

<p>IRAK4-IN-9 is a potent IRAK4 inhibitor with an IC50 of 1.5 nM, promising for inflammatory, autoimmune diseases, and cancer research.</p>

<p>STING agonist-7 is an agonist of non-nucleotide STING that binds selectively to mouse STING but not human STING [1].</p>

<p>BMY-25551, a Mitomycin A analog, exhibits cytotoxicity 8 to 20 times greater than Mitomycin C against both murine and human tumor cell lines. It is applicable in research pertaining to cancer and hematological disorders.</p>

<p>TLR4/NF-κB/MAPK-IN-1 is a novel antineuroinflammatory agent that functions by inhibiting the TLR4/NF-κB/MAPK pathways.</p>

<p>IRAK4-IN-18: Potent IRAK4 inhibitor (IC50: 15 nM), reduces IL23 in cells, prevents rat arthritis.</p>

<p>ZM514 inhibits CD73 (hCD73 IC50: 1.39 μM, mCD73 IC50: 14.65 μM) with low cytotoxicity, suitable for cancer research.</p>

<p>(S)-MALT1-IN-5: Potent MALT1 protease inhibitor, may help in abnormal T/B-cell signalling and MALT1-linked diseases.</p>

<p>Carazostatin is an antioxidant, free radical scavenger, and potent lipid peroxidation inhibitor.</p>

<p>Galectin-3-IN-2 inhibits galactose lectin-3 (Gal-3) with an 8.3 μM IC50, impacting cancer-related metabolism.</p>

<p>HEI3090 is an activator of the P2X7R receptor. This compound enhances the production of IL-18 by stimulating dendritic cells that express P2X7R, which in turn promotes the production of IFN-γ by natural killer cells and CD4T cells within tumors, triggering a sustained anti-tumor response. Additionally, HEI3090 can be used to improve the efficacy of αPD-1 therapy in non-small cell lung cancer (NSCLC).</p>

<p>Glutathione monoethyl ester, a derivative of glutathione, can protect motor neuron cells (NSC-34) from TDP-43 pathology caused by mutations, which includes reducing aggregate formation, nuclear clearance, reactive oxygen species (ROS) production, and cell death.</p>

<p>NDT-30805, a triazolopyridine, blocks IL-1β in PBMC (IC50: 0.013μM) &amp; NLRP3 inflammasome, for inflammation research.</p>

<p>Pelecopan (BCX9930), an oral complement factor D inhibitor, prevents hemolysis in PNH (IC50=14.3 nM).</p>

<p>Keap1-Nrf2-IN-5 is a potent inhibitor of Keap1-Nrf2 PPI (Keap1-Nrf2 protein-protein interaction) (IC50: 4.1 μM, Kd: 3.7 μM).</p>

<p>NLRP3-IN-69 (Compound 23) inhibits the activation of NF-κBp65 and the formation of the NLRP3 inflammasome. It suppresses the overexpression of IL-1β, iNOS, and COX-2 induced by LPS, and inhibits the production of NO (IC50=5.66 μM), thereby demonstrating anti-inflammatory activity.</p>

<p>COX-2-IN-51 (E25) is a potent COX-2 inhibitor with an IC50 of 70.7 nM. It significantly suppresses LPS-induced release of NO and PGE2, the expression of COX-2 and iNOS, and the activation of the NF-κB pathway. Displaying anti-inflammatory and analgesic effects in various mouse models through NF-κB pathway inhibition, COX-2-IN-51 has lower gastrointestinal side effects compared to Indomethacin.</p>

<p>BMS-986458 is a highly selective, orally active BCL6 PROTAC degrader. It specifically targets cereblon (CRBN) and the BCL6 N-terminal BTB domain to catalyze proximity-induced BCL6 degradation. BMS-986458 is applicable for research in B-cell non-Hodgkin lymphoma.</p>

<p>STING-IN-11 (Compound 42) is an orally active STING inhibitor with an IC50 of 37.8 nM. It impedes palmitoylation of the STING protein and the downstream signaling of STING, thereby inhibiting STING-mediated inflammation. STING-IN-11 demonstrates good in vivo safety and can be utilized for research on STING-related inflammatory and autoimmune diseases.</p>

<p>OP-5244 has comparable potency to bisphosphonic acid series and targets CD73.</p>

<p>COX-2-IN-7: potent, orally active COX-2 inhibitor with higher selectivity than Celecoxib, IC50 6.585 uM, anti-inflammatory, low ulcer risk.</p>

<p>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.</p>

<p>HG-12-6 is a type II IRAK4 inhibitor, targeting its inactive form with an IC50 of 165 nM, and is used in autoimmunity and inflammation.</p>

<p>STAT1/3-IN-1 (Compound 6k) is an inhibitor of STAT1/3 phosphorylation. It prevents the phosphorylation and nuclear translocation of STAT1/3. Additionally, STAT1/3-IN-1 inhibits the inflammatory enzymes iNOS and COX-2. This compound exhibits anti-inflammatory properties by reducing pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, without significant cytotoxicity.</p>

<p>20-Hydroxyvitamin D3 (20(OH)D3) is a hydroxy metabolite of vitamin D3. It functions as a ligand for the vitamin D receptor (VDR), aryl hydrocarbon receptor (AhR), liver X receptor (LXR), and retinoic acid receptor-related orphan receptor (ROR). 20-Hydroxyvitamin D3 inhibits cell proliferation and induces differentiation. It is applicable in research on inflammatory and autoimmune diseases.</p>

<p>Potent oral AHR antagonist with IC50 &lt; 0.5 μM, hinders tumor growth with anti-PD-1.</p>

<p>CD73-IN-7: potent inhibitor of CD73, blocks adenosine production to treat tumors.</p>

<p>Heme Oxygenase-2-IN-1 is a selective HO-2 inhibitor with IC50s: 14.9 μM (HO-1), 0.9 μM (HO-2).</p>

<p>Hetrombopag olamine is a non-peptide thrombopoietin (TPO) receptor agonist with oral activity.</p>

<p>RuDiOBn exhibits low antioxidant activity by scavenging DPPH and ABTS free radicals with scavenging rates of 13.2% and 5.9% at a concentration of 100 μg/mL. It inhibits collagen glycation and reduces the formation of advanced glycation end-products (AGE) with an IC50 of 2.45 μg/mL. RuDiOBn also enhances fibroblast proliferation and migration, stimulates collagen synthesis, and aids in skin repair and regeneration while inhibiting collagenase.</p>

<p>MAO-B-IN-7 inhibits MAO-B/AChE, crossing the blood-brain barrier; IC50: 41/87 nM (h/eel AChE), 0.3 μM (MAO-B). Reduces oxidative stress and neuroinflammation.</p>

<p>ODN 21158 is a potent, non-cytotoxic inhibitor of G-modified TLR3 and TLR9. ODN 21158 dose-dependently inhibits IFN-α secretion.</p>

<p>IRAK4-IN-14 is a selective, potent, orally active IRAK4 inhibitor (IC50: 0.003 μM) with favorable PK parameters in rats and mice. effect.</p>

<p>NP3-146 sodium is an inhibitor of the NLRP3 inflammasome.</p>

<p>NLRP3-IN-58 (Compound DS15) acts as an inhibitor of NLRP3 inflammasome activation, with an IC50 value of 3.85 μM, and is capable of inhibiting 33% of IL-1β release at a concentration of 10 μM.</p>

<p>IRAK4-IN-19, an IRAK4 inhibitor (IC50: 4.3 nM), hampers IL23 synthesis and arthritis progression.</p>

<p>C5aR-IN-3, a potent C5aR inhibitor, may treat autoimmune and inflammatory diseases.</p>

<p>Ocadusertib is an effective inhibitor of the serine/threonine kinase receptor-interacting protein kinase 1 (RIPK1).</p>

<p>NLRP3-IN-56 (compound 062) is an inhibitor of NLRP3. It effectively suppresses the secretion of IL-1β in THP-1 cells, demonstrating an IC50 of 9.7 nM. NLRP3-IN-56 is useful for research into NLRP3-mediated symptoms and/or diseases.</p>

<p>CD73-IN-13, a potent CD73 inhibitor, may be developed for tumor-related disease treatment.</p>

<p>RGT-068A is a potent, selective and oral bioavailable MALT1 inhibitor .</p>

<p>OP-5244 sodium: potent oral CD73 inhibitor (IC50: 0.25 nM), potential in cancer research by hindering adenosine, reversing immunosuppression.</p>

<p>OxLig-1 (7-Ketocholesteryl-9-carboxynonanoate) constitutes a lipid component of oxidized low-density lipoprotein (oxLDL) and serves as a critical ligand for β-glycoprotein I (β(2)-GPI). It induces nuclear translocation by activating the NF-κB pathway. Additionally, oxLig-1 is utilized in the study of atherosclerosis (AS).</p>

<p>Compound 16c, an imidazoquinoline, is a TLR7/8 agonist; IC50: 3.91 μM (TLR7), 2.19 μM (TLR8); targets TLR-2050 for disease treatment.</p>