Imunologia e Inflamação

<p>TLR7/8 antagonist 2: potent, orally active, IC50: 4.9 nM (TLR7), 0.6 nM (TLR8); potential for lupus therapy research.</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>IACS-8779 is a potent STING agonist that efficiently stimulates interferon gene activity and exhibits strong systemic antitumor effects.</p>

<p>NLRP3-IN-4 is an effective, oral NLRP3 inflammasome inhibitor with potent anti-inflammatory effects on colitis.</p>

<p>IL-17 modulator 5 is a IL-17 inhibitor, with an IC 50 of 1 nM .</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>K-14585 blocks PAR(2), reduces NFkappaB activity, and IL-8 response, but alone can boost IL-8.</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>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>TLR7/8 agonist 7 activates immune cells, useful in ISAC synthesis and immunity research.</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>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>ROS inducer 9 (compound 4e) is an antibacterial agent with a minimum inhibitory concentration (MIC) of 0.25 μg/mL against Escherichia coli. It eradicates bacteria by inhibiting GSH activity and increasing ROS levels. Additionally, ROS inducer 9 exhibits low toxicity toward red blood cells and RAW 264.7 cells.</p>

<p>CVN293 is a inhibitor of the potassium channel KCNK13,BBB,It inhibits the production of the pro-inflammatory cytokine IL-1β induced by NLRP3 in microglia</p>

<p>Heme Oxygenase-1-IN-2 is a novel inhibitor of heme oxygenase-1 (HO-1), displaying potent antiproliferative activity in vitro, with an IC50 value of 0.95 μM.</p>

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

<p>Anti-inflammatory agent 102 (Compound 11a) is an orally effective anti-inflammatory compound. It exerts its effects by inhibiting the activation of the ASK1/p38 MAPKs/NF-κB signaling pathway. This agent displays significant anti-inflammatory activity by suppressing the release of NO, ROS, and inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Anti-inflammatory agent 102 is applicable in research concerning inflammatory diseases, including ulcerative colitis (UC).</p>

<p>MALT1-IN-5 is a potent inhibitor of the MALT1 protease and can be used in cancer research.</p>

<p>Itaconic acid prodrug-1 (Compound P2) is an orally active prodrug of Itaconic acid that efficiently delivers Itaconic acid to skin tissues upon oral administration. It exhibits immunomodulatory effects, significantly inhibiting Poly(I:C)/IFNγ-induced inflammatory cytokines in human epidermal keratinocytes. Itaconic acid prodrug-1 is useful for research into alopecia areata and other inflammatory skin conditions.</p>

<p>COX-2-IN-12: Potent, selective COX-2 inhibitor, IC50=19.98μM, safe anti-inflammatory with low acute toxicity.</p>

<p>ODN 2088 is a potent inhibitor of TLR3, TLR7 and TLR9 that is non-cytotoxic and shows inhibition of the release of IFN-α and IL-6.</p>

<p>Corannulene is an agonist of the aromatic hydrocarbon receptor (AhR). It induces a lower cytotoxic response in liver cancer cells compared to Benzo[a]pyrene and shows potential for use in cancer research.</p>

<p>MAY0132 is a potent and selective EPAC2 inhibitor with an IC50 of 0.4 μM. It significantly inhibits the replication of HMPV, AdV, and RSV, reduces cytokine/chemokine production induced by viral infections, and suppresses NF-κB activation. MAY0132 exhibits antiviral activity and can be used in respiratory virus infection research.</p>

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

<p>NDT-30805, a triazolopyridine, blocks IL-1β in PBMC (IC50: 0.013μM) &amp; NLRP3 inflammasome, for inflammation research.</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>NLRP3-IN-8, orally active inflammasome blocker, IC50 of 1.23μM, stable (t1/2 = 138.63min), non-toxic (IC50 &gt;100μM).</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>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>MPGES-1, potential anti-inflammatory drug target, has IC50 of 0.03 μM with mPGES-1-IN-1.</p>

<p>COX-2-IN-13 is a potent, selective COX-2 inhibitor with 0.98 μM IC50; shows strong anti-inflammatory properties and low acute toxicity.</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>Ambuic acid: cyclohexanone with antifungal, quorum-inhibiting, antibacterial properties, blocks cyclic peptides; reduces MRSA abscesses in mice.</p>

<p>COX-2-IN-10 is a potent COX-2 inhibitor, reducing IL-6, TNF-α, IL-1β, PGE2 (IC50=2.54 μM), and iNOS expression.</p>

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

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

<p>IRAK4-IN-18: Potent IRAK4 inhibitor (IC50: 15 nM), reduces IL23 in cells, prevents rat arthritis.</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>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>ND-2158 is a potent and selective inhibitor of IRAK4.</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>CD73-IN-2 is a potent inhibitor of CD73 (IC50: 0.09 nM).</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>Rafutrombopag is a thrombopoietin (TPO) agonist.</p>