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>