systemic lupus erythematosus

Frentizole, an immunosuppressive agent, is an inhibitor of the Aβ-ABAD interaction

Resiquimod (R848) is an agonist of Toll-like receptors 7 and 8 (TLR7/TLR8) that induces the upregulation of cytokines including TNF-α, IL-6, and IFN-α. It possesses immunomodulatory, antitumor, and antiviral activities, and can be used to induce models of myocarditis and systemic lupus erythematosus (SLE).

Paquinimod (ABR 25757) is a S100A9 inhibitor preventing S100A9 binding to TLR-4.

TLR7/8/9 antagonist 2 is an orally active and highly bioavailable vTLR7/8/9 antagonist. It inhibits HEK/hTLR7, HEK/hTLR8, and HEK/hTLR9 with IC50s of 0.011 μM, 0.029 μM, and 0.052 μM, respectively. TLR7/8/9 antagonist 2 can be used to study auto-inflammatory diseases such as systemic lupus erythematosus or lupus nephritis.

Feeblin(IRF5-IN-1) is a protein degradation inducer that specifically blocks pro-inflammatory signaling pathways associated with autoimmune diseases and can be used to study immune system disorders in the class of systemic lupus erythematosus.

Mefloquine (Ro 215998), a quinoline antimalarial agent, is an anti-SARS-CoV-2 entry inhibitor. Mefloquine is also a K+ channel (KvQT1/minK) antagonist with an IC50 of ~1 μM. Mefloquine can be used for malaria, systemic lupus erythematosus, and cancer research.

Prednisolone hemisuccinate is a soluble glucocorticoid and cortisol, a prodrug of the glucocorticoid (GR) agonist Prednisone, which exerts anti-inflammatory, immunosuppressive, and antiallergic effects by binding to GR receptor, and is commonly used in systemic lupus erythematosus, acute dermatologic conditions, and arthritis.

(S)-Dexfadrostat ((S)-Fadrozole), an aromatase inhibitor, exhibits an IC 50 of 4.6 nM in in vitro assays using human placental microsomes. It is applicable for research on estrogen-dependent breast cancer, gynecomastia, and systemic lupus erythematosus.

(S)-Hydroxychloroquine ((S)-HCQ) sulfate is an isomer of Hydroxychloroquine. At concentrations of 2.5-20 mg/mL, (S)-Hydroxychloroquine sulfate can reduce the rate of insulin degradation in liver homogenates isolated from both non-diabetic and diabetic rats. Preparations containing Hydroxychloroquine have been used in studies of malaria, rheumatoid arthritis, and systemic lupus erythematosus.

KV1.3-IN-2 (Compound I) selectively inhibits the kv1.3 potassium channel without affecting the hERG channel. It is applicable in research related to immune-associated diseases such as psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.

Syk-IN-13 is a Syk inhibitor that can be utilized in research related to rheumatoid arthritis and/or systemic lupus erythematosus.

KBD4466 is a potent oral inhibitor of TLR7 and TLR8, with IC50 values of 0.9 nM and 2.8 nM, respectively. This compound effectively suppresses the inflammatory cytokines IL-6 and IFN-α. KBD4466 has shown to improve disease progression and increase survival rates in the BXSB/MpJ mouse model of systemic lupus erythematosus (SLE). It is suitable for research into autoimmune diseases.

H-151 Alkyne (Compound H-151-AL) is a selective inhibitor of STING (stimulator of interferon genes). It shows promise for research in autoimmune diseases, including systemic lupus erythematosus, scleroderma, and autoinflammatory diseases.

Steroid sulfatase-IN-10 (Example 216) is a potent inhibitor of steroid sulfatase, with an IC50 range of 0.03-0.27 µM. It is applicable in research on inflammatory diseases such as rheumatoid arthritis, type 1 and type 2 diabetes, and systemic lupus erythematosus.

TLR9 antagonist1 (Compound 38) is a selective TLR9 inhibitor with an IC50 of 0.1 nM for hTLR9, demonstrating superior antagonistic activity compared to hTLR2/4/5/7/8. This compound exacerbates disease symptoms in mouse models of systemic lupus erythematosus (SLE) and raises levels of anti-dsDNA and anti-Sm antibodies. TLR9 antagonist1 is applicable in research on inflammatory and immune diseases such as lupus and arthritis.

ETI60 is an orally active selective TLR inhibitor that targets the nucleoside-binding sites I of TLR7 (IC50 = 0.68 μM) and TLR9 (IC50 = 0.12 μM) without affecting surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4, and TLR5). It demonstrates nanomolar activity in cell-based, biophysical, and in vivo assays, effectively inhibiting endosomal TLR-mediated pro-inflammatory signaling. ETI60 modulates the expression of genes related to inflammation and significantly improves symptoms in mouse models of psoriasis and systemic lupus erythematosus (SLE). ETI60 is applicable in studies related to autoimmune and inflammatory diseases.

ETI41 is an orally active selective TLR inhibitor that targets the nucleoside-binding site I of TLR7 (IC50= 0.63 μM) and TLR9 (IC50= 0.16 μM), without affecting surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4, and TLR5). It demonstrates nanomolar activity in cell-based, biophysical, and in vivo studies, effectively inhibiting endosomal TLR-mediated pro-inflammatory signaling. ETI41 suppresses the expression of inflammation-related genes and significantly improves symptoms in mouse models of psoriasis and systemic lupus erythematosus (SLE). ETI41 is applicable in research related to autoimmune and inflammatory diseases.

UM-203 is a reversible covalent STING antagonist effective against both mouse and human STING. It is particularly potent in inhibiting the common human STINGR232 variant. UM-203 prevents STING oligomerization and decreases the phosphorylation of downstream TBK1 and IRF3, thereby blocking the signaling pathways mediated by IRF3 and NF-κB, and inhibiting the secretion of IFNβ and IL-6. UM-203 is useful for research in inflammation and immunology, such as systemic lupus erythematosus.

YE6144 free base is a selective prototype inhibitor of interferon regulatory factor 5 (IRF5). It has demonstrated the ability to suppress disease progression in mouse models of systemic lupus erythematosus (SLE) and is particularly effective in maintaining remission. This compound can be utilized for SLE research.

Paramethasone Acetate is a synthetic glucocorticoid with anti-inflammatory and immunosuppressive effects that can be used in the treatment of systemic lupus erythematosus.

Solcitinib (GLPG-0778) (GSK2586184, GLPG0778) is a JAK1 inhibitor. Solcitinib may be potentially used for the treatment of psoriasis, ulcerative colitis, and systemic lupus erythematosus.

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.

PAD-IN-2 is a potent inhibitor of pad4 with an IC50 value <1 μM and can be used to study autoimmune diseases and cancers such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, cutaneous lupus erythematosus, cystic fibrosis, ulcerative colitis, asthma, multiple sclerosis, and psoriasis.

(R)-Elsubrutinib ((R)-ABBV-105) is a Btk inhibitor and an isomer of Elsubrutinib, suitable for inflammation research.