Immunology and Inflammation

<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>NLRP3-IN-8, orally active inflammasome blocker, IC50 of 1.23μM, stable (t1/2 = 138.63min), non-toxic (IC50 &gt;100μM).</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>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>(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>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>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>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>COX-2-IN-12: Potent, selective COX-2 inhibitor, IC50=19.98μM, safe anti-inflammatory with low acute toxicity.</p>

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

<p>TLR7/8 agonist 7 activates immune cells, useful in ISAC synthesis and immunity research.</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>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>iNOS/PGE2-IN-1: iNOS/PGE2 inhibitor, reduces LPS-induced NO, low ulcer risk, anti-inflammatory.</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>Hypoxystat increases the affinity of hemoglobin for oxygen, thereby reducing the release of oxygen to tissues and inducing tissue hypoxia. [Hypoxystat] can alleviate mitochondrial disorder Leigh syndrome in Ndufs4 gene knockout mouse models. Hypoxystat is orally active.</p>

<p>PB01 is a DPP-4 inhibitor with an IC50 of 15.66 nM. It effectively suppresses high glucose-induced ROS generation and mitochondrial superoxide production while significantly reducing the cellular expression of DPP-4. Additionally, PB01 notably lowers blood glucose levels in diabetic mice. It demonstrates excellent safety, exhibiting almost no cytotoxicity at a concentration of 100 μM. PB01 holds promise for research in the diabetes field.</p>

<p>A-9758: RORγt selective inverse agonist, IC50 5nM, inhibits IL-17A, Th17, and treats psoriasis.</p>

<p>MG-T-19, a TIM-3 inhibitor, inhibit the interaction of TIM-3 with PtdSer, CEACAM1, and Gal-9, and increased the production of TNF-α and IFN-γ in PBMCs.</p>

<p>4-Octylphenol is an endocrine disruptor with gender-specific effects on male germ cells, significantly reducing the mitotic index and the number of spermatogonia. It also causes inflammatory damage in the gills of carp by activating the complement system through the C3a/C3a receptor (C3a/C3aR) axis and C5a/C5a receptor 1 (C5a/C5aR1) axis. Furthermore, 4-Octylphenol induces immune suppression by disrupting the balance between helper T (Th) cells 1/Th2 and regulatory T (Treg)/Th17 cells, and triggers inflammatory damage through the Toll-like receptor 7 (Toll-like Receptor (TLR))/inhibitor κBα/nuclear factor κB (TLR7/IκBα/NF-κB) pathway.</p>