inflammatory bowel diseases

Tert-butyl 4-[[1-[(4-chlorophenyl)methyl]-3-hydroxy-2-oxopyridin-4-yl]methyl]piperazine-1-carboxylate inhibit of human recombinant EGLN-1 as substrate after 20 mins by mass spectrophotometric analysis.

Elubrixin (SB-656933) inhibits neutrophil CD11b upregulation (IC50 of 260.7 nM) and shape change (IC50 of 310.5 nM). Elubrixin can be used for inflammatory diseases such as inflammatory bowel disease and airway inflammation. Elubrixin is a potent, selective, competitive, reversible and orally active CXCR2 antagonist and an IL-8 receptor antagonist.

Vercirnon (Traficet-EN) is a selective and potent antagonist of CCR9 (IC50: 10 nM). It is also used in the research of inflammatory bowel diseases.

L-Homocysteine is a biological thiol involved in various diseases and pathological conditions. It is a marker for atherosclerosis and can exacerbate intestinal inflammation in inflammatory bowel disease (IBD) by promoting the expression of 5-LOX and COX-2, making it suitable for inducing vascular endothelial inflammation models.

4-Iodobutyl benzoate is structurally related to bicyclic heterocyclic compounds such as indole and indoline. It functions as a metabolite of drug amides and is utilized in the treatment of inflammatory bowel disease, degenerative diseases, and intestinal disorders. 4-Iodobutyl benzoate inhibits the activity of proteolytic enzymes by binding to their active sites.

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.

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).

IRAK4 modulator-2 (Compound 5) is a selective dual inhibitor of IRAK4 and IRAK1, with IC₅₀ values of 0.005 μM and 0.97 μM respectively. It may be employed in research concerning autoimmune and inflammatory diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

Spns2-IN-3 (compound 510) is an SPNS2 inhibitor with an IC50 value of 1.2 μM for hSPNS2. It is applicable in research on autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD), as well as fibrosis, muscle atrophy, metastasis, acute lung injury, rheumatoid arthritis, colitis, Alzheimer's disease, and other conditions linked to SPNS2 activity.

RORγt inverse agonist 35 (Compound 22) is an RORγt inverse agonist with an IC50 of 1.51 μM. It significantly inhibits Th17 differentiation and pro-inflammatory characteristics in human CD4+ T cells. This compound can be utilized for research on Th17-driven autoimmune diseases, such as psoriasis, multiple sclerosis, and inflammatory bowel disease (IBD).

NLRP3-IN-81 (N102) is an inhibitor capable of crossing the blood-brain barrier, effectively countering NLRP3 inflammasome-dependent pyroptosis with an EC50 of 0.029 μM for Nigericin-induced pyroptosis. It significantly suppresses caspase-1 activation and IL-1β release that depend on NLRP3. Additionally, NLRP3-IN-81 disrupts the interaction between NLRP3 and the adaptor protein ASC, while inhibiting ASC oligomerization. This compound is applicable in research on pyroptosis-related diseases, such as inflammatory bowel disease and type 2 diabetes.

HDAC6-IN-54 (Compound 9m) is a highly selective inhibitor of HDAC6 (histone deacetylase 6), with an IC50 value of 0.021 μM. It prevents the activation of the NLRP3 inflammasome, providing relief from symptoms associated with NLRP3 inflammasome-related diseases such as acute peritonitis, inflammatory bowel disease, and psoriasis.

Keap1-IN-2 (Compound 164) is an inhibitor of KEAP1 with an IC50 of 2 nM. It indirectly activates Nrf2 by blocking KEAP1, thereby enhancing cellular antioxidant capacity. By preventing KEAP1-mediated degradation of Nrf2, Keap1-IN-2 promotes the accumulation and nuclear translocation of Nrf2. This compound is used in research on diseases related to oxidative stress, such as inflammatory bowel disease, Crohn's disease, and ulcerative colitis, which are immune-related conditions.

DDS5 acts as a CD28 inhibitor with a kd of 175.57 µM. It significantly inhibits the interaction between CD28 and CD80, with an IC50 of 332 µM. DDS5 is applicable in research related to immune-mediated diseases, such as inflammatory bowel disease and rheumatoid arthritis.

Tapinarofprodrug-1 (Compound 31) is an orally active prodrug of Tapinarof, which acts as an AhR agonist. It has shown efficacy in improving conditions in a TNBS-induced mouse model of inflammatory bowel disease and can be utilized in the study of inflammatory diseases.

Linvemastat (Compound FC-4) is an orally active MMP-12 inhibitor with an IC50 of less than 10 nM and demonstrates high selectivity over MMP-1, -2, -3, -7, -9, -10, and -14. It significantly reduces lung fibrosis in a mouse model of bleomycin-induced unilateral pulmonary fibrosis and effectively alleviates kidney damage, interstitial inflammation, or fibrosis in a unilateral ureteral obstruction renal fibrosis model. Linvemastat is suitable for research into inflammatory diseases such as idiopathic pulmonary fibrosis (IPF), inflammatory bowel disease (IBD), and asthma.

JAK1-IN-18 (Example 2) is a selective JAK1 inhibitor with an IC50 value of 0.15 nM, demonstrating significantly greater inhibitory potency for JAK1 compared to JAK2 and JAK3. It significantly reduces inflammation in ulcerative colitis (UC) mouse models induced by DSS and Crohn's disease (CD) rat models induced by DNBS. JAK1-IN-18 is applicable for research into autoimmune diseases (such as inflammatory bowel disease), viral infections (such as hepatitis B virus infection), and cancers (such as hematologic malignancies).

GCS-12-6 is a potent Th2-selective NKT cell agonist that targets the CD1d protein. It holds potential for research in autoimmune diseases, such as inflammatory bowel disease and multiple sclerosis.

PHD2-IN-6 (Example 89) is an inhibitor of HIF prolyl hydroxylase 2 (PHD2) with an IC50 of 31.6 nM. This compound can stimulate the production of the gene encoding erythropoietin (EPO). PHD2-IN-6 is applicable in research on inflammatory diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis.

AS2795440 is a PIKfyve inhibitor. It selectively suppresses the production of pro-inflammatory cytokines such as IL-12p40 and IL-6 and the activation of B cells, without affecting Ca2+ signaling. In a mouse model of adjuvant-induced arthritis (AIA), AS2795440 significantly reduces joint inflammation and bone loss. This compound is useful for researching inflammatory and autoimmune diseases like rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

2,6-Dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide (GDC046), a potent lead analog, has good kinase selectivity, physicochemical properties and pharmacokinetic profile.

Elubrixin tosylate (SB-656933 tosylate) is a high-potency, selective, competitive, and reversible CXCR2 and IL-8 receptor antagonist. It effectively inhibits neutrophil CD11b upregulation (IC50 of 260.7 nM) and shape change (IC50 of 310.5 nM). This compound holds promise for studying inflammatory diseases, including inflammatory bowel disease and airway inflammation.

TCJL37, a potent, selective, and orally bioavailable inhibitor of TYK2, exhibits a K i value of 1.6 nM. It is useful for researching inflammatory bowel diseases (IBD) [1].

CCR6 antagonist 1, a chemical compound acting as a CCR6 antagonist, effectively inhibits the CCL20/CCR6 axis. Its utility lies in research focused on autoimmune-mediated inflammatory diseases, including inflammatory bowel diseases (IBDs).