TLR7/8-IN-1, a crystalline TLR7/TLR8 inhibitor, is a valuable compound for autoimmune disease research[1].

(S)-AK-242 ((S)-Resatorvid) is a cytokine inhibitor used in the treatment of heart disease, autoimmune disease, and inflammatory disease.

CP-456773 (MCC950 (CP-456773) and CRID3) is an effective and specific cytokine release inhibitor and NLRP3 inflammasome inhibitor. CP-456773 inhibits IL-1β secretion and caspase 1 processing. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced IL-1β production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis.

TNF-α-IN-8 (compound I-42) is an isoindole-imide-based inhibitor of tumor necrosis factor-alpha (TNF-α) with applications in researching various diseases including cancer, heart disease, osteoporosis, and autoimmune disorders. Additionally, this compound serves as a click chemistry reagent, possessing an Azide group that can participate in copper-catalyzed azide-alkyne cycloaddition (CuAAc) or strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Alkyne, DBCO, or BCN groups.

Omega-3 Arachidonic Acid ethyl ester, a rare polyunsaturated fatty acid with limited presence in dietary sources, is crucial for infant growth and development and offers protection against heart disease, blood clots, high blood pressure, and inflammatory and autoimmune disorders. In human platelet membranes, it impedes arachidonyl-CoA synthetase, exhibiting a Ki of 14 μM, and shows similar inhibitory effects on arachidonoyl-CoA synthetase in calf brain extract with an IC50 of roughly 5 μM. The ethyl arachidonate derivative offers enhanced lipophilicity compared to its free acid counterpart.

IRG1-IN-1 is an itaconic acid derivative with the ability to inhibit the activity of Immune Response Gene 1 (IRG1) and is suitable for use in the field of cancer, inflammation and autoimmune disease research.

BDC2.5 Mimotope 1040-63 is a biologically active peptide employed in the investigation of type 1 diabetes (T1D), an autoimmune disease where T cells induce destruction of pancreatic islet β cells. This mimotope, originating from the TCR transgenic model (BDC2.5), facilitates the examination of antigen presentation mechanisms to islet autoantigen-specific T cells, contributing to the understanding of T cell-mediated beta-cell damage due to autoreactive T cell responses.

MP-PEG8-Val-Lys-Gly-7-MAD-MDCPT is an agent-linker conjugate designed for antibody-drug conjugate (ADC) applications, with potential use in cancer and autoimmune disease research.

Canakinumab (ACZ885) is a recombinant human IL-1β-targeting monoclonal antibody.Canakinumab has been shown to inhibit human and chorioallantoic monkey IL-1β, with IC50 values of 43.6 and 40.8 pM, respectively.Canakinumab has anti-inflammatory activity, inhibiting inflammation associated with autoimmune diseases by neutralizing IL-1β signaling. Canakinumab has anti-inflammatory activity, inhibiting inflammation associated with autoimmune diseases by neutralizing IL-1β signaling.Canakinumab has been used for the treatment of gout and coronary artery disease.

Dalazatide (ShK-186) TFA, a precise Kv1.3 potassium channel peptide inhibitor, is employed in researching autoimmune conditions, including multiple sclerosis (MS), lupus erythematosus, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease [1] [2] [3].

Bromodomain Inhibitor-12 Edisylate (example 303) serves as a bromodomain inhibitor applicable to autoimmune and inflammatory disease research [1].

PROTAC TYK2 Degradation Agent1 is a potent, subtype-selective degrader of TYK2, exhibiting degradation activity with a DC50 of 14 nM. It is utilized in autoimmune disease research [1].

ARN-6039 is an orally available inverse agonist of RORγ for Autoimmune Neuroinflammatory Demyelinating Disease. The activity of ARN-6039 against RORγ was demonstrated in a RORγ-activated IL-17A Prom/LUCPorter assay in HEK 293 cells (360 nM) and in IL-17 r

Dalazatide (ShK-186) is a specific inhibitor of the Kv1.3 potassium channel, employed in researching autoimmune conditions including multiple sclerosis (MS), lupus erythematosus, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease [1] [2] [3].

AcylCoA:cholesterol acyltransferase (ACAT) is an intracellular cholesteryl ester synthase tied closely to the absorption of dietary cholesterol. Oleyl analide (OA) is a weak inhibitor of acylCoA:cholesterol acyltransferase (ACAT) with an IC50 of 26 μM. OA and the related glyceride dioleoyl phenylamino propane 1,2-diol have been linked to a syndrome of eosinophilia, excessive T-cell activation, and elevated interleukin-4 (IL-4), soluble IL-2R, and IL-5. The clinical consequences are an acute pulmonary inflammatory reaction followed by chronic neuropathy, myalgia, and autoimmune connective tissue disease, generally referred to as toxic oil syndrome (TOS). Aniline-denatured cooking oil is a source of OA associated with TOS.

Angiogenin (108-122) is an angiogenin peptide. Angiogenin (108-122) acts as a therapeutic agent for the prophylaxis and/or treatment of cancer, an infectious disease, a fibrotic disease, an inflammatory disease, a neurodegenerative disease, an autoimmune

BMS-986143, an orally active, reversible BTK inhibitor with an IC50 value of 0.26 nM, is designed for autoimmune disease research. Additionally, it targets TEC, BLK, BMX, TXK, FGR, YES1, and ITK, exhibiting IC50s of 3 nM, 5 nM, 7 nM, 10 nM, 15 nM, 19 nM, and 21 nM, respectively [1].

Esculentoside A can suppress inflammatory responses in LPS-induced ALI through inhibition of the NF-κB and mitogen-activated protein kinase signaling pathways. Esculentoside A may be useful for the treatment of autoimmune disease through modulation on T c

Amdizalisib is a PI3K inhibitor and used for the research of inflammatory disease, autoimmune disease or cancer.

Cletoquine oxalate (Desethylhydroxychloroquine oxalate) is a major active metabolite of Hydroxychloroquine. Cletoquine has the ability to against the chikungunya virus (CHIKV). Cletoquine has antimalarial effects and has the potential for autoimmune disea

HS-243 is an inhibitor of IRAK-4 and IRAK-1 with IC50s of 20 and 24 nM. HS-243 shows anti-inflammatory and anticancer activity.

c-Fms-IN-14 (Example 76) is a potent inhibitor of the c-Fms kinase with an IC50 of 4 nM, utilized in cancer and autoimmune disease research [1].

Ciamexon (Ciamexone) is a novel immunomodulator that has shown promising results in experimental models of autoimmune disease with little demonstrated cytotoxicity.Ciamexon can be used to study endocrine ophthalmopathies and diabetes mellitus, with slight improvement in ophthalmic disease following short-term administration.

KZR-616, a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 has the potential for the research of multiple autoimmune diseases[1][2]. KZR-616 also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). KZR-616 maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. KZR-616 (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].KZR-616 is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 and PR-924 [3]. KZR-616 (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1]. [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.

JPE-1375, a complement C5a receptor 1 (C5aR1) antagonist, effectively inhibits polymorphonuclear leukocyte mobilization (EC50=6.9 µM) and reduces TNF levels (EC50=4.5 µM) in mice, making it useful for autoimmune and inflammatory disease research [1].

Tibulizumab (LY 3090106), a tetravalent bispecific monoclonal antibody, selectively binds to B-cell activating factor (BAFF) and IL-17A with dissociation constants (Kd) of 60 pM and 14 pM, respectively. This specificity renders it a valuable tool for autoimmune disease research.

Angiogenin (108-122) TFA is an angiogenin peptide.Angiogenin (108-122) acts as a therapeutic agent for the prophylaxis and/or treatment of cancer, an infectious disease, a fibrotic disease, an inflammatory disease, a neurodegenerative disease, an autoimmu

SSAO inhibitor-3 (Compound 2) can be used in the study of atherosclerosis, diabetes and its complications, obesity, stroke, chronic kidney disease, retinopathy, chronic obstructive pulmonary disease (COPD), autoimmune diseases, multiple sclerosis, etc. SSAO inhibitor-3 is an inhibitor of semicarbazide-sensitive amine oxidase (SSAO) with IC 50 s of 0.1-10 μM and <10 nM for human AOC1 and SSAO, respectively [1].

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine tightly binds to TNF-α and blocks its interaction with TNFR1, with an IC50 value of 0.109 μM. Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research[1]. Benpyrine (5-20 μM; 14 hours; RAW264.7 cells) pretreatment results in a dose-dependent decrease in the phosphorylation of IκBα in RAW264.7 cells (stimulated with 10 ng/mL TNF-α or 1 μg/mL LPS). Benpyrine abolishes the TNF-α-induced nuclear translocation of NF-κB/p65 in RAW264.7 cells[1].Benpyrine only blocks cell death induced by TNF-αWT and Y119A, and increases the cell survival rate up to 80%. Benpyrine does not obviously affect L57A- and Y59L-induced cytotoxicity in L929 cells[1]. Benpyrine (25-50 mg/kg; oral gavage; daily; for 2 weeks; Balb/c mice) treatment significantly relieves the symptoms of collagen-induced arthritis. Benpyrine dose-dependently decreases the levels of proinflammatory cytokines, such as IFN-γ, IL-1β and IL-6, and increases the concentration of the anti-inflammatory cytokine IL-10[1].Endotoxemia murine model shows that Benpyrine (25 mg/kg) could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury[1]. [1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.

Cletoquine is a major active metabolite of Hydroxychloroquine. Cletoquine has the ability to against the chikungunya virus (CHIKV). Cletoquine has antimalarial effects and has the potential for autoimmune disease treatment.

ML604440 is a cell permeable proteasome β1i (LMP2) subunit inhibitor.

TR-14035 (MDK-1191) is a dual antagonist of α4β7/α4β1 integrins (IC50s: 7/87nM).

Commendamide (N-acyl-3-hydroxypalmitoyl-glycine) is a newly discovered GPCR G2A/GPR132 agonist (EC50=11.8 μM) that isolated from Bacteroides vulgatus. [1] G2A/GPR132 belongs to the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. GPR132/G2A is first reported to be a transcriptional target for BCR-ABL tyrosine kinase attenuating B-cell expansion in vitro and arresting cells at G2 during mitosis. It has been involved in autoimmune disease and atherosclerosis. [1] Commendamide and structurally related endogenous long-chain N-Acyl-amides activates discrete human receptors. In a screen for agonist activity against a library of 242 GPCRs, commendamide is found to activate a single receptor G2A/GPR132. This activity is confirmed by a synthetic sample of commendamide. Commendamide analogs with changes in the head group or acyl chain also exhibited reduced GPR132/G2A activity. [1]

6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2. It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells. 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes. In vivo, 6(5H)-phenanthridinone reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels.

Briakinumab (ABT-874), a fully human anti-IL-12/23p40 monoclonal antibody, selectively targets and neutralizes IL-12 and IL-23. This compound is utilized in the research of various autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis [1].

hGPR91 antagonist 3 is an orally active, potent, and selective hGPR91 antagonist. hGPR91 antagonist 3 is used to study hypertension, autoimmune diseases, and retinal angiogenesis. hGPR91 antagonist 3 has been shown to be effective in the treatment of hypertension, autoimmune disease, and retinal angiogenesis.

Vidofludimus hemicalcium (4sc-101; SC12267) is an orally active compound that acts as a dihydroorotate dehydrogenase (DHODH) inhibitor and serves as a novel modulator of the farnesoid X receptor (FXR). This immunomodulatory agent is utilized in the research of autoimmune disorders, including inflammatory bowel disease (IBD), and is explored for its potential in fatty liver disease research through FXR targeting.

SSAO inhibitor-2 (Compound 1) can be used in the research of atherosclerosis, diabetes and its complications, obesity, stroke, chronic kidney disease, retinopathy, chronic obstructive pulmonary disease (COPD), autoimmune diseases, multiple sclerosis, etc. SSAO inhibitor-2 is the inhibitor of semicarbazide-sensitive amine oxidase (SSAO) with IC 50 s <10 nM and 10-100 μM for human SSAO and MAO-A, respectively [1].

AKP-11 is a sphingosine-1-phosphate receptor 1 (S1P1) agonist with an EC50 of 0.047 μM for [35S]GTPγS binding to CHO-K1 cell membranes expressing human S1P1. It reduces S1P1 surface expression and enhances Akt and ERK phosphorylation in CHO cells with S1P1-HA at a 100 nM concentration. At doses of 1.3 and 3 mg/kg, AKP-11 lowers IFN-γ and IL-17 protein levels in the spinal cord and mitigates disease severity in a rat experimental autoimmune encephalomyelitis (EAE) model. Additionally, it decreases peripheral total lymphocyte and specific T cell subsets (CD4+, CD8+, and CD26L+ T cells) counts in both EAE rats and healthy controls at a 1.3 mg/kg dosage.

Tapinarof (Benvitimod) is targeted as a topical cream treatment for psoriasis, a chronic autoimmune skin disease.

Compound I (S1P1 agonist 6) is an S1P1 agonist that mitigates autoimmune activity by inhibiting lymphocyte trafficking and has potential as an immunosuppressive agent in autoimmune disease research [1].

AC430 is a potent and specific small molecule inhibitor of janus kinase 2 (JAK2), which has been implicated as a target for therapy in both oncology and autoimmune disease. AC430 is currently being developed by Ambit. In preclinical studies, AC430 has exhibited potency against JAK2 and V617F mutated JAK2 in cell-based models that is at least equivalent to, and in most cases superior to, competing JAK2 inhibitors. In preclinical oncology and autoimmune models, AC430 is well tolerated and has significant efficacy at oral doses as low as 10 mg/kg/day.

L-Mevalonic acid ((S)-Mevalonic acid), a distant precursor of cholesterol, is a metabolite of the mevalonic acid pathway and is used in the study of autoimmune diseases, atherosclerosis and Alzheimer's disease.

C5aR-IN-3, a potent C5aR inhibitor, holds potential for inflammation disease research due to its ability to counteract increased C5a levels, which are linked to autoimmune and inflammatory disorders.

Spermidine trihydrochloride (4-Azaoctamethylenediamine trihydrochloride), a natural polyamine, is a novel autophagy inducer and negatively modulates N-methyl-d-aspartate (NMDA).

Spermidine (N-(3-Aminopropyl)-1,4-diaminobutane) inhibits NOS1 (nNOS). Spermidine binds and precipitates DNA and may be used for purification of DNA binding proteins. Spermidine activates PNK (polynucleotide kinase T4). Spermidine binds to and activates NMDA and has been shown to potentiate NMDA-induced currents in a concentration-dependent manner.