autoimmune disease

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.

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.

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

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.

Cletoquine oxalate (Desethylhydroxychloroquine oxalate) is a major active metabolite of Hydroxychloroquine, with antiviral efficacy against the chikungunya virus (CHIKV), antimalarial effects, and potential for treating autoimmune diseases.

HPN-01 (IKK inhibitor XII) is a selective IKK inhibitor that inhibits IKK-α, IKK-β, and IKK-ε. HPN-01 reduces the severity of the disease, attenuates the immune imbalance, and prolongs the lifespan of mice in a model of autoimmune encephalomyelitis, and can be used to study immune disorders.

Nrf2 activator-12 (compound 10v) effectively activates Nrf2 (EC50=83.5 nM) and exhibits favorable pharmacological properties. It reverses disease progression and alleviates demyelination in a mouse model of experimental autoimmune encephalomyelitis.

ERAP1-IN-3 (compound 13) is a potent inhibitor of endoplasmic reticulum aminopeptidase 1 (ERAP1), with a pIC50 value of 8.6. ERAP1-IN-3 shows potential for research in cancer immunotherapy and autoimmune disease studies.

STAT4-IN-1 is a STAT4 inhibitor with a Ki of 0.35 μM. It holds promise for research into autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and diabetes.

TNF-α-IN-24 (Example 15) is a TNF-α inhibitor with an IC50 value of 4.1 nM. It is applicable in research on inflammatory and autoimmune diseases such as rheumatoid arthritis and Crohn's disease.

SCH-900875 is an orally active, brain-penetrant, and selective inhibitor of the CXCR3 receptor, demonstrating significant selectivity towards CXCR1 and CXCR2 receptors as well. By binding to CXCR3, SCH-900875 blocks the ligands CXCL9, CXCL10, and CXCL11, thereby inhibiting downstream G protein and β-arrestin signaling pathways and reducing inflammation cell migration. This compound holds potential for research into autoimmune diseases (such as rheumatoid arthritis and multiple sclerosis) and inflammatory conditions (such as psoriasis and inflammatory bowel disease).

ARN-6039, an orally available inverse agonist of RORγ, targets Autoimmune Neuroinflammatory Demyelinating Disease. Its efficacy was demonstrated in a RORγ-activated IL-17A Prom LUCPorter assay in HEK 293 cells (360 nM) and in IL-17 release from CD4+T cell assays (220 nM).

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.

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM and an IC50 value of 0.109 μM. It tightly binds to TNF-α, blocking its interaction with TNFR1, and has potential for TNF-α mediated inflammatory and autoimmune disease research [1].

MCC950 (CP-456773) is a NLRP3 inflammasome inhibitor (IC50=7.5-8.1 nM). MCC950 can be used to treat inflammatory diseases, inflammation-related tumors and neurodegenerative diseases.

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.

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.

TLR7/8-IN-1, a crystalline TLR7/TLR8 inhibitor from patent WO2019220390 (compound 2b), is a valuable compound for autoimmune disease research.

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

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].

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

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

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

SSAO inhibitor-2 (Compound 1) is an inhibitor of semicarbazide-sensitive amine oxidase (SSAO) with IC50 values <10 nM for human SSAO and 10-100 μM for MAO-A, respectively [1]. It 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, and multiple sclerosis.