Immunology and Inflammation

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.

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.

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

mPGES1-IN-9 (compound 1_8) is an mPGES1 inhibitor with an IC50 of 0.5 μM and is utilized in anti-inflammatory research.

Compound 6, an AhR agonist, selectively activates the aryl hydrocarbon receptor (AhR) with an EC50 of 0.01 nM [1].

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

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.

Factor B-IN-6 is an orally bioavailable inhibitor of Factor B. It exhibits significant inhibitory activity on the activation of the human serum alternative pathway. In model animals, Factor B-IN-6 can improve kidney lesions and function, reducing urinary protein levels. Factor B-IN-6 is applicable for kidney disease research.

α-Glucosylrutin is an effective antioxidant known for its activity in scavenging free radicals. Due to its high epidermal bioavailability, it is commonly utilized in studies related to skin aging.

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.

COX-2-IN-47 (compound 6c) is a selective inhibitor of COX-2, exhibiting an IC50 of 0.03 μM. This compound also displays antiedema activity.

NLRP3-IN-6 (Compound 34) is a selective inhibitor of the NLRP3 inflammasome.

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.

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

AM679 is a potent, selective FLAP inhibitor with strong leukotriene suppression in vivo, minimal CYP3A4 interaction, and excellent pharmacokinetics in rodent models.

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.

NLRP3-IN-8, orally active inflammasome blocker, IC50 of 1.23μM, stable (t1/2 = 138.63min), non-toxic (IC50 >100μM).

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

FK-565 is a ligand of nucleotide-binding oligomerization domain-1 (NOD1) that induces a mouse model of arteritis.

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

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

AS2690168 freebase is an orally active inhibitor of RANKL signaling, capable of suppressing RANKL-induced osteoclastogenesis in RAW264 cells. AS2690168 is applicable in research related to pathological bone resorption.

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.

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.

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

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

Ambuic acid: cyclohexanone with antifungal, quorum-inhibiting, antibacterial properties, blocks cyclic peptides; reduces MRSA abscesses in mice.

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.

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.

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

MGD-28 is a Cullin-CRBN-dependent IKZF family protein degrader for IKZF1 (Ikaros), IKZF2 (Helios), IKZF3 (Aiolos) ,and CK1α, antiproliferative.

Fluopimomide (LH2010A), a powerful insecticide, is extensively utilized in the control of agricultural pests. It adversely affects the growth, locomotor behavior, reproduction, and lifespan of nematodes. Concurrently, it leads to increased production of reactive oxygen species (ROS), accumulation of lipids and lipofuscins, as well as a rise in malondialdehyde content. Additionally, Fluopimomide inhibits the antioxidant system of nematodes.

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.

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

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

ZMC3 (NSC328784), a zinc chelator, exhibits properties as a zinc metallochaperone. It shows enhanced sensitivity in cells with the p53-R175H mutation and increases the cellular levels of ROS (reactive oxygen species).

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).

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

Imipramine Blue chloride is an effective anti-invasive agent capable of inhibiting glioma invasion. It suppresses the production of reactive oxygen species (reactive oxygen species) mediated by NADPH oxidase.

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

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

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

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

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

Carazostatin is an antioxidant, free radical scavenger, and potent lipid peroxidation inhibitor.

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

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

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

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

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.

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].

TLR7/8 agonist 13 is an orally active dual agonist of TLR7 (with a lowest effective concentration (LEC) [hTLR7] of 1.6 μM) and TLR8 (LEC [hTLR8] of 1.6 μM). It acts on human peripheral blood mononuclear cells (hPBMC) with agonistic activity (LEC [hPBMC] = 0.5 μM). In mice and cynomolgus monkeys, TLR7/8 agonist 13 induces endogenous IFNα, activates myeloid dendritic cells and monocytes, promoting their differentiation towards a TH1 phenotype. In chronic AAV-HBV mouse models, it reduces viral load and HBV surface antigen levels. TLR7/8 agonist 13 has the potential to indirectly induce IFNγ, facilitating the response of HBV antigen-specific CD8 T cells. This compound is useful for hepatitis B virus research.

mPGES1-IN-5 (compound 18) is a multi-substituted pyrimidine compound that acts as a submicromolar inhibitor of PGE2 production. It primarily exerts its anti-inflammatory effects by inhibiting mPGES-1 and demonstrates significant inhibitory activity in vivo against acute inflammation models.

Izicopan (INF056) is an antagonist of the complement factor C5a receptor. It inhibits C5a-induced calcium mobilization with an IC50 ranging from 10 to 100 nM.

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

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).

Nrf2-ARE/hMAO-B/QR2 modulator 1 a resveratrol derivative activated the NRF2-ARE inhibit hMAO-B and QR2, promote hippocampal neurogenesis Alzheimer's disease .

GNE-2256 is an orally active IRAK4 inhibitor with nanomolar binding affinity, supporting studies of inflammatory and innate immune signaling.

Heme Oxygenase-1-IN-3 (compound 4) serves as a potent and selective inhibitor of heme oxygenase-1 (HO-1) with a dissociation constant (Kd) of 141 nM, making it suitable for use in cancer and neurodegenerative disease research.

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

(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).

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.

NP3-146 sodium is an inhibitor of the NLRP3 inflammasome.

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].

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.

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.

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.

(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).

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

IRAK4-IN-12 (compound 37) is a potent inhibitor of IRAK4 (IC50: 0.015 μM) with cellular pIRAK4 potency (IC50: 0.5 μM).

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

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.

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].

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.

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].

TLR7/8 antagonist 2: potent, orally active, IC50: 4.9 nM (TLR7), 0.6 nM (TLR8); potential for lupus therapy research.

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].

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].

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).

IKZF1-degrader-1 (Compound 9-B) serves as a potent degrader of the IKZF1 protein, exhibiting a DC50 of 0.134 nM. It is applicable in the degradation of tumors [1].

RIPK2-IN-6 (Compound 15a) is an inhibitor of RIPK that specifically targets the phosphorylation of RIPK2, thereby suppressing the NF-κB and MAPK signaling pathways. It has demonstrated anti-inflammatory and anti-fibrotic activities in a mouse model of colitis induced by Dextran sodium sulfate.

Polvitolimod is a TLR7 agonist used to treat infectious disease and cancer.

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

Galectin-3-IN-4 (compound 5), a carboxamide analog, effectively and selectively inhibits both human and mouse galectin-3. This compound demonstrates notable potency with IC50 values of 21 nM for hGal-3 and 167 nM for mGal-3. It is also orally bioavailable. For other galectins, Galectin-3-IN-4 shows IC50 values of 1580 nM for hGal-1 and 2750 nM for hGal-9, respectively [1].

Ac5GalNTGc, an analog of hexosamine, inhibits mucin-type O-linked glycosylation biosynthesis [1].

MMG-11 quarterhydrate, a potent hTLR2 antagonist, inhibits TLR2/1 and TLR2/6 with IC50s of 1.7μM and 5.7μM; low toxicity.

Cyclic-di-IMP (C-di-IMP), a STING agonist, serves as a research tool in tumor studies.

STING-IN-11 is a potent, orally bioavailable STING inhibitor (IC₅₀ = 37.8 nM) that blocks STING protein palmitoylation and downstream signaling.

Compound 8, an AhR agonist 7, demonstrates potent activation of AhR with an EC50 of 13nM [1].

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.

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.

Galectin-3-IN-3 (Compound 4) serves as a selective and orally active inhibitor targeting Gal-3. It exhibits IC50 values of 11 nM for mGal-3 and 84 nM for hGal-3 [1].

STING agonist-21 (compound 1), possessing an EC 50 of 592.8 nM, functions as a STING agonist. It is applicable in cancer research [1].

Balsalazide disodium is an aminosalicylate prodrug that releases mesalamine in the colon, providing diverse anti-inflammatory effects in regions affected by colitis. Additionally, it exhibits anticancer properties by modulating the IL-6/STAT3 pathway.

ALR-27 serves as an antagonist of the 5-lipoxygenase (5-LOX) activating protein FLAP and exhibits anti-inflammatory properties. It effectively inhibits 5-LOX product formation (>80%) in pro-inflammatory M1-MDM without significantly inhibiting 5-LOX directly. Additionally, ALR-27 decreases prostaglandin and leukotriene (LT) production in neutrophils and enhances the production of specialized prolytic mediators in certain human macrophage phenotypes [1].

IKZF2-degrader 1 (Compound 31) is a molecular glue-type degrader of IKZF2 with a DC50 of 0.5 nM. It exhibits relatively low degradation activity against CK1α, with a DC50 of 210 nM. This compound is applicable in research focused on IKZF2-dependent cancers.

TE-11 is a MIF tautomerase inhibitor with an IC50 of 5.63 μM. This compound can alleviate Crohn's-like colitis, reduce MIF-induced migration of eosinophils and neutrophils, and prevent M1 polarization and associated metabolic reprogramming.

SB24011, a STING-TRIM29 interaction inhibitor, has an IC₅₀ value of 3.85 μM. It boosts STING immunity by upregulating STING protein levels, thereby enhancing the immunotherapeutic effects of STING agonists and anti-PD-1 antibodies through systemic anticancer immunity [1].

(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.