Immunology and Inflammation

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.

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].

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

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

STING agonist-20: potent, aids in XMT-2056 synthesis, used as a cancer vaccine adjuvant.

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.

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

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].

LD03-DEX is a precursor compound of dexamethasone, characterized by its immunosuppressive activity.

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.

SMW139 is a selective allosteric antagonist of the P2X7 receptor, exhibiting a Ki value of 32 nM for human P2X7R. In rat liver microsomes, its half-life is 47 minutes. SMW139 is applicable in research related to inflammation, Alzheimer's disease, and multiple sclerosis.

IRAK4-IN-15: selective IRAK4 inhibitor, IC50 0.002 μM, good PK, low clearance, synergizes with Acalabrutinib in MyD88/CD79 mutant ABC-DLBCL.

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).

Cyazofamid functions as a fungicide by impairing the production of ATP. It inhibits Organic Cation Transporter 3 (OCT3) and OAT1 with IC50 values of 1.54 and 17.3 μM, respectively.

CD73-IN-18 (compound 35j) is an orally effective inhibitor of the extracellular 5'-nucleotidase (CD73) enzyme. It can be utilized in anticancer research.

Creatine ethyl ester (CEE) is a readily available form of creatine commonly used in supplements. It can upregulate TLRs (TLR2, 3, 4, and TLR7) over a short period.

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.

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].

UM-3006 is a potent TLR7/8 agonist that enhances immune responses by activating the TLR signaling pathway. This compound holds significant research and application potential in the fields of vaccine adjuvants and immune diseases.

<p>EGR-1-IN-3 (Compound 36) is an inhibitor of early growth response 1 (EGR-1) binding to DNA. It effectively suppresses the binding of EGR-1 to DNA and the expression of inflammation-related genes (such as TSLP, IL-31, IL-6, and CCL2) induced by TNFα. This compound is applicable to the study of inflammatory diseases.</p>

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.

Compound WK692 (compund WK692) is a BCL6 inhibitor that effectively suppresses the growth of diffuse large B-cell lymphoma cells without toxic side effects and acts synergistically with inhibitors of EZH2 and PRMT5.

Gardiquimod (hydrochloride) is an imidazoquinoline class TLR7/8 agonist. It can inhibit HIV-1 infection in macrophages and activated peripheral blood mononuclear cells (PBMCs). At concentrations below 10 μM, Gardiquimod (hydrochloride) specifically activates TLR7.

MSA-2 dimer: selective oral non-nucleotide STING agonist, Kd=145 μM, long-term antitumor effect, non-covalent, higher permeability.

Benzimidazothiazole-derived Compound 28 from tilomisole targets COX-2, has potent anti-inflammatory effects & is orally bioavailable.

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.

BCL6ligand-4 is a BCL6 ligand used in the synthesis of PROTACs, such as BCL6PROTAC 1.

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

SP4206 is an interaction inhibitor of IL-2/IL-2Rα (IL-2 and IL-2Rα with Kd of 70 nM and 10 nM,respectively)

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

LHC-165 is an agonist of TLR7. It also has the potential to treat solid tumors.

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.

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].

Z-Val-Val-Nle-diazomethylketone is an inhibitor of cathepsin S (CATS). It significantly suppresses the upregulation of IFNg-induced MHCII molecules, specifically HLA-DR and Ii-p33/35, while increasing the protein level of Ii-p10. This compound can be utilized for research into skin disorders such as psoriasis, atopic dermatitis, and actinic keratosis.

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 .

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

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

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

Anti-osteoporosis agent-11 (compound 3k) is an anti-osteoporosis compound targeting osteoclasts. It exhibits its most prominent effect by inhibiting osteoclast differentiation, with an IC50 value of 0.36 μM. Additionally, Anti-osteoporosis agent-11 suppresses osteoclast formation, bone resorption, and the expression of osteoclast-specific genes by blocking the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.

KCC2 Modulator-2 (example 53) is a regulator of KCC2 with an EC50 of 0.215 μM. It is used in the research of neurological diseases.

dCK1α-2 is an orally effective CK1α molecular glue (Molecular Glue) degrader that targets p53 pathway-related targets. It demonstrates antitumor efficacy in mouse models by enhancing the expression of p53-related genes.

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

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

RIPK1-IN-19 is a selective and potent RIPK1 inhibitor that protects against cell necrosis in the tnf α-induced SIRS model and IMQ-induced psoriasis model.

SLC7A11-IN-2 (Compound 1) is an inhibitor of SLC7A11/xCT. It disrupts the oxidative balance in HeLa cells by decreasing intracellular glutathione levels and increasing oxidative stress, thereby inducing cell death with an IC50 of 10.23 μM. Molecular dynamics simulations have demonstrated that SLC7A11-IN-2 exhibits a stronger binding affinity to SLC7A11 compared to Erastin. This compound is useful for research in the field of cervical cancer.

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

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

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].

MGD-4 is an orally active, Cereblon (CRBN)-dependent degrader of IKAROS proteins that demonstrates dose-dependent degradation of IKZF1 (DC50=67.2 nM), IKZF2 (DC50=918.2 nM), and IKZF3 (DC50=95.8 nM). The compound effectively inhibits the growth of multiple myeloma.

Cbl-b-IN-1 is a potent Cbl-b inhibitor (IC50 <100 nM) with potential anticancer activity for the study of intestinal inflammation.

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

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.

(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).

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.

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.

Lobaric acid, from Stereocaulon lichen, has antioxidant and anticancer properties, inhibits PTP1B and 12(S)-LOX, and reduces TMV lesions in plants.

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].

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.

AS2690168 hydrochloride is an orally active inhibitor of RANKL signaling that can suppress RANKL-induced osteoclastogenesis in RAW264 cells. AS2690168 is applicable in research related to pathological bone resorption.

(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.

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

IRAK1/4/pan-FLT3 Kinase-IN-2 (compound 27) is a potent dual inhibitor of IRAK1/4 and FLT3 with IC50 values of 10 nM, 0.7 nM, and < 0.5 nM, respectively. This compound enhances survival in mice models of acute myeloid leukemia.

Pentacyclic triterpene, anti-inflammatory agent 12, inhibits LPS inflammation (IC50: 2.22 μM). May benefit inflammatory disease studies.

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

PSMA-IN-4 (compound 9) functions as a potent PSMA inhibitor, exhibiting an IC 50 value of 1.2 μM [1].

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

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

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

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.

PZ-3022 is an orally active, conformational PanK activator that counteracts C3-CoA inhibition. In a mouse model of propionic acidemia, it elevates hepatic CoASH and C2-CoA levels while reducing C3-CoA, making it useful for studying mitochondrial defects in propionic acidemia.

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

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

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

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).

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

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

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].

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.

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

ROS151 is an AChE inhibitor with IC50 values of 14 nM (hAChE), 1.68 μM (eqBChE), and 8.17 μM (hFAAH). Additionally, it acts as a chelating agent for Fe3+ and Cu2+. ROS151 is utilized in research related to Alzheimer's disease.

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

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

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

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>CD73-IN-19 (Compound 4ab) is an inhibitor of CD73, demonstrating a 44% inhibition rate of CD73 enzyme activity at 100 μM. It entirely counters T cell proliferation blockade triggered by TCR activation (induced by CD73 activity) at 10 μM and 100 μM and inhibits hA2A receptor activity in HEK-293 cells with a Ki of 3.31 μM. CD73-IN-19 holds potential for research in the field of immune diseases.</p>

IRAK4-IN-31 is a crystalline inhibitor of IRAK4. It is applicable in research related to myelodysplastic syndromes (MDS).

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

Factor B-IN-4 is a potent inhibitor (IC50: 1 μM) of complement factor B. Factor B-IN-4 can be used to study inflammatory and immune-related diseases.

Anti-inflammatory agent 18: NO activity blocker (IC50: 15.94 μM), hampers HMGB1-induced inflammation, potential for COVID-19, sepsis study.

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.

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

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

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

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.

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

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

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.

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).